Prognostic roles of diabetes mellitus and hypertension in advanced hepatocellular carcinoma treated with sorafenib

Abstract

Background & aims It remains limited whether diabetes mellitus (DM) and hypertension (HTN) affect the prognosis of advanced hepatocellular carcinoma (HCC) treated with sorafenib. Our study attempted to elucidate the roles of DM/HTN and the effects of diabetes medications among advanced HCC patients receiving sorafenib. Methods From August 2012 to February 2018, 733 advanced HCC patients receiving sorafenib were enrolled at China Medical University, Taichung, Taiwan. According to the presence/absence of DM or HTN, they were divided into four groups: control [DM(-)/HTN(-), n = 353], DM-only [DM(+)/HTN(-), n = 91], HTN-only [DM(-)/HTN(+), n = 184] and DM+HTN groups [DM(+)/HTN(+), n = 105]. Based on the types of diabetes medications, there were three groups among DM patients (the combined cohort of DM-only and DM+HTN groups), including metformin (n = 63), non-metformin oral hypoglycemic agent (OHA) (n = 104) and regular insulin (RI)/neutral protamine hagedorn (NPH) groups (n = 29). We then assessed the survival differences between these groups. Results DM-only and DM+HTN groups significantly presented longer overall survival (OS) than control group (control vs. DM-only, 7.70 vs. 11.83 months, p = 0.003; control vs. DM+HTN, 7.70 vs. 11.43 months, p = 0.008). However, there was no significant OS difference between control and HTN-only group (7.70 vs. 8.80 months, p = 0.111). Besides, all groups of DM patients showed significantly longer OS than control group (control vs. metformin, 7.70 vs. 12.60 months, p = 0.011; control vs. non-metformin OHA, 7.70 vs. 10.80 months, p = 0.016; control vs. RI/NPH, 7.70 vs. 15.20 months, p = 0.026). Conclusions Rather than HTN, DM predicts better prognosis in advanced HCC treated with sorafenib. Besides, metformin, non-metformin OHA and RI/NPH are associated with longer survival among DM-related advanced HCC patients receiving sorafenib.

Clinicopathological Aspects and Inflammation-Immune Markers in Alcohol and/or Hepatitis C Virus-Induced Hepatocellular Carcinoma Patients Treated With Sorafenib

“…The associations of high AFP level and Child-Pugh B or C with low OS in our patients were not a surprise. High AFP level was previously associated with low survival rates in patients with HCC induced mainly by HBV and/or HCV treated with sorafenib [13,14,16,18,19]. Previous studies have shown that the time required for the tumor to double in volume, as well as the time for AFP levels to double, were shorter in HCC with higher degrees of malignancy [37].…”

“…DM predicted a better prognosis in HCC treated with sorafenib in two studies [19,20]. Since hyperglycemia favors glycolysis which is a main energy-producing process in cancer cells [35], the authors attributed the association of DM2 with longer survival of HCC patients treated with sorafenib to the effects of TKIs in glycemic control in diabetics reducing proliferation of the malignant cells.…”

“…It was already postulated that clinicopathological aspects, such as age [9], performance status [9][10][11][12][13], non-viral etiologies [9], Child-Pugh score [10][11][12][13][14][15][16][17], alpha-foetoprotein (AFP) level [13,14,16,18,19], type 2 diabetes mellitus (DM2) [19,20], sarcopenia [21], and tumor size/volume [18,19] are independent prognostic factors for HCC patients treated with sorafenib, AFP Level and Child-Pugh Score in HCC Prognosis Gastroenterol Res. 2024;17 (1): [23][24][25][26][27][28][29][30][31] but most of these associations need to be confirmed.…”

Does Type 2 Diabetes Increase the Risk of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease Patients: A Systematic Review

“…Many risk determinants of HCC have already been discussed such as the etiology of cirrhosis, age, gender, race, body mass index (BMI), diabetes, and hepatitis C virus (HCV) genotype [ 4 ]. The occurrence of HCC in diabetes mellitus is most likely related at both molecular and epidemiological levels [ 5 ]. A recent study evidenced that diabetes is associated with a three-fold higher risk for HCC in NAFLD [ 1 ].…”

“…Geriatric patients who have a low level of serum albumin should be carefully monitored for HCC [ 1 ]. Elderly people have been correlated with HCC incidence which shows the importance of comorbidity management because of the greater incidence of comorbidities, such as diabetes mellitus and hypertension, in the older population [ 5 ]. In 2018, neoplasm in the liver is found as the sixth most frequent and prevailing cause of cancer-related deaths globally with approximately 841,000 new cases and 782,000 deaths in which HCC is the most common [ 5 ].…”