Obesity and Hepatocellular Carcinoma: A Complex Relationship

Henry, Zachary; Caldwell, Stephen H.

doi:10.1053/j.gastro.2015.05.024

Cited by 7 publications

(2 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HCC incidence and its main risk factors show notable disparities across countries [ 3 , 4 ]. In the United States, an increasing rate of HCC is associated with alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), metabolic syndrome and hepatitis C virus infection (HCV) [ 2 , 5 ], all of which are directly associated with dyslipidemia [ 5 , 6 , 7 , 8 ]. In Egypt and China, chronic liver disease (CLD) is the main risk factor of HCC [ 4 , 9 ] due to HCV and hepatitis B virus infection (HBV).…”

Section: Introductionmentioning

confidence: 99%

Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma

Ismail

Elfert

Helal

et al. 2020

Cancers

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma

Ismail

Elfert

Helal

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Thus, the similarity of T2D profile at baseline across three race/ethnic groups were limited to being insulin naïve, under reasonable glycemic control, and without a history of cancer, CVD, and CLD. While the relationship between individual level BMI and HCC is well‐established yet complex, our data from EMR however fell short to reveal a clinically significant association between BMI with HCC nor the variation of BMI between race/ethnic groups. This could have an implication on the extent to which the confounding associated BMI could be addressed.…”

Section: Discussionmentioning

confidence: 73%

Metformin modifies disparity in hepatocellular carcinoma incidence in men with type 2 diabetes but without chronic liver diseases

et al. 2019

View full text Add to dashboard Cite

Background We assessed racial/ethnic disparity in hepatocellular carcinoma (HCC) incidence among men with type 2 diabetes (T2D) but without chronic liver diseases (CLD), and whether metformin use modified the disparity. Methods Study cohort: the nationwide Veterans Administration Health Care System electronic medical records among 40‐89 years old men with T2D; without CLD, cancer, cardiovascular or renal diseases previously; insulin and thiazolidinedione naive. Logistic regression analyses compared HCC incidence between race/ethnicity groups under no metformin use adjusted for covariates and inverse propensity score weights (IPSW) for race/ethnicity. The generalizability technique integrated with IPSW was incorporated to compare covariates adjusted odds ratios (aOR) of HCC associated with metformin use among race/ethnicity groups. Results Study cohort: N = 84 433; 79.47% non‐Hispanic white (NHW), 15.5% non‐Hispanic African American (NHAA), 5.03% Hispanics; 36.76% metformin users; follow‐up 6.10 ± 2.87 years; age 67.8 ± 9.8 years, HbA1c 6.57 ± 0.98%; 0.14% HCC cases. Under no metformin use, HCC incidence was lower for NHAA vs NHW (aOR = 0.60 [0.40‐0.92]), similar between NHW and Hispanics. Metformin was associated with reduced HCC risk: aOR = 0.57 (0.40‐0.81) for NHW; aOR = 0.35 (0.25‐0.47) for NHAA; aOR = 0.31 (0.22‐0.43) for Hispanics. Metformin dose >1000 mg/d was neutral for NHW; less effective for NHAA (P = 0.02); more effective for Hispanics (P = 0.002). Conclusions In men with T2D but without CLD nor metformin use, HCC incidence was lower for NHAA compared to NHW or Hispanics; similar between NHW and Hispanics. Metformin use reduced HCC risk and modified the race/ethnicity disparity. Impact Metformin's heterogeneous HCC prevention effect elucidates potential interventions to modify HCC disparity in patients with T2D.

show abstract

Obesity and Hepatocellular Carcinoma: Epidemiology and Mechanisms

Akkız

2021

Liver Cancer in the Middle East

View full text Add to dashboard Cite

Obesity and Hepatocellular Carcinoma: A Complex Relationship

Cited by 7 publications

References 23 publications

Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma

Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma

Metformin modifies disparity in hepatocellular carcinoma incidence in men with type 2 diabetes but without chronic liver diseases

Obesity and Hepatocellular Carcinoma: Epidemiology and Mechanisms

Contact Info

Product

Resources

About