Identification of predictive factors for post-transarterial chemoembolization liver failure in hepatocellular carcinoma patients: A retrospective study.

BACKGROUND: Post-transarterial chemoembolization (TACE) liver failure occurs frequently in hepatocellular carcinoma (HCC) patients. The identification of predictors for post-TACE liver failure is of great importance for clinical decision-making in this population. AIM: To investigate the occurrence rate and predictive factors of post-TACE liver failure in this retrospective study to provide clues for decision-making regarding TACE procedures in HCC patients. METHODS: The clinical records of HCC patients treated with TACE therapy were reviewed. Baseline clinical characteristics and laboratory parameters of these patients were extracted. Logistic models were used to identify candidates to predict post-TACE liver failure. RESULTS: A total of 199 HCC patients were enrolled in this study, and 70 patients (35.2%) developed post-TACE liver failure. Univariate and multivariate logistic models indicated that microspheres plus gelatin embolization and main tumor size > 5 cm were risk predictors for post-TACE liver failure [odds ratio (OR): 4.4, 95% confidence interval (CI): 1.2-16.3, P = 0.027; OR: 2.3, 95%CI: 1.05-5.3, P = 0.039, respectively]. Conversely, HCC patients who underwent tumor resection surgery before the TACE procedure had a lower risk for post-TACE liver failure (OR: 0.4, 95%CI: 0.2-0.95, P = 0.039). CONCLUSION: Microspheres plus gelatin embolization and main tumor size might be risk factors for post-TACE liver failure in HCC patients, while prior tumor resection could be a favorable factor reducing the risk of post-TACE liver failure.

Firmicutes and Blautia in gut microbiota lessened in chronic liver diseases and hepatocellular carcinoma patients: a pilot study.

The gut microbiota system plays a vital role in liver diseases. This study aimed to address the diversity of gut microbiota and its correlations with clinical parameters in healthy individuals, chronic liver disease (CLD), and hepatocellular carcinoma (HCC) patients. Fecal specimens of nine healthy individuals, 11 CLD, and 21 HCC were collected. The diversity of gut microbiota was examined by PCR and Illumina MiSeq sequencing and analyzed using 16S rRNA gene sequencing database. The correlations between gut microbiota and the clinical parameters of participants were also addressed. Compared to healthy individuals, Firmicutes at a phylum level decreased in CLD and HCC patients and Proteobacteria increased (p < 0.05). The composition of Blautia on a genus level in CLD and HCC patients significantly decreased compared to healthy controls (p < 0.05). Firmicutes composition was negatively associated with age and number of males (p < 0.05) and was positively associated with monocytes, high-density lipoprotein cholesterol (HDL-C), and estimated glomerular filtration rate (eGFR) levels (p < 0.05). At a genus level, Blautia composition was negatively associated with cirrhosis, age, and number of males (p < 0.01), while it was positively associated with red blood cells (RBCs), triglycerides, HDL-C, and lymphocyte levels (p < 0.05). Conclusively, there was a significant compositional difference in gut microbiota in CLD and HCC patients compared with healthy subjects. Firmicutes and Blautia in gut microbiota system lessened in CLD and HCC patients. Clinical biochemical parameters have an impact on the diversity of gut microbiota in liver diseases.

Predictors for imaging progression on chest CT from coronavirus disease 2019 (COVID-19) patients.

OBJECTIVE: This study aimed to investigate the potential parameters associated with imaging progression on chest CT from coronavirus disease 19 (COVID-19) patients. RESULTS: The average age of 273 COVID-19 patients enrolled with imaging progression were older than those without imaging progression (p = 0.006). The white blood cells, platelets, neutrophils and acid glycoprotein were all decreased in imaging progression patients (all p < 0.05), and monocytes were increased (p = 0.025). The parameters including homocysteine, urea, creatinine and serum cystatin C were significantly higher in imaging progression patients (all p < 0.05), while eGFR decreased (p < 0.001). Monocyte-lymphocyte ratio (MLR) was significantly higher in imaging progression patients compared to that in imaging progression-free ones (p < 0.001). Logistic models revealed that age, MLR, homocysteine and period from onset to admission were factors for predicting imaging progression on chest CT at first week from COVID-19 patients (all p < 0.05). CONCLUSION: Age, MLR, homocysteine and period from onset to admission could predict imaging progression on chest CT from COVID-19 patients. METHODS: The primary outcome was imaging progression on chest CT. Baseline parameters were collected at the first day of admission. Imaging manifestations on chest CT were followed-up at (6±1) days.

Add-On Therapy with Traditional Chinese Medicine Improves Outcomes and Reduces Adverse Events in Hepatocellular Carcinoma: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Traditional Chinese medicine (TCM) therapy for hepatocellular carcinoma remains controversial. This study aimed to evaluate the efficacy and safety of TCM regimens in HCC treatment. METHODS: Randomized controlled trials (RCTs) up to June 1, 2016, of the TCM treatment for hepatocellular carcinoma were systematically identified in PubMed, CNKI, Ovid, Embase, Web of Science, Wanfang, VIP, CBM, AMED, and Cochrane Library databases. RESULTS: A total of 1010 and 931 patients in 20 RCTs were randomly treated with add-on TCM therapy and conventional therapy, respectively. The additional use of TCM significantly improved six-month, one-year, two-year, and three-year overall survival rates in HCC cases (RR = 1.3, P = 0.01; RR = 1.38, P = 0.0008; RR = 1.44, P < 0.0001; RR = 1.31, P = 0.02, resp.). Add-on TCM therapy significantly increased PR rate and total response rate (tRR) and reduced PD rate compared to those in control group (34.4% versus 26.3%, RR = 1.30, P = 0.002; 41.6% versus 31.0%, RR = 1.30, P < 0.0001; and 16.6% versus 26.5%, RR = 0.64, P < 0.0001, resp.). Additionally, TCM combination therapy significantly increased the quality of life (QOL) improvement rate and reduced adverse events including leukopenia, thrombocytopenia, anemia or erythropenia, liver injury, and gastrointestinal discomfort in HCC patients (all P < 0.05). CONCLUSION: Add-on therapy with TCM could improve overall survival, increase clinical tumor responses, lead to better QOL, and reduce adverse events in hepatocellular carcinoma.

Naturally occurring basal core promoter A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma: a meta-analysis.

Basal core promoter (BCP) A1762T/G1764A dual mutations in hepatocarcinogenesis remain controversial. Published studies up to June 1, 2015 investigating the frequency of A1762T/G1764A dual mutations from chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma (HCC), were systematically identified. A total of 10,240 patients with chronic HBV infection, including 3729 HCC cases, were included in 52 identified studies. HCC patients had a higher frequency of BCP A1762T/G1764A dual mutations compared with asymptomatic HBsAg carriers (ASC) and patients with chronic hepatitis B (CHB) and liver cirrhosis (LC) (OR = 5.59, P < 0.00001; OR = 2.87, P < 0.00001; OR = 1.55, P = 0.02, respectively). No statistically significant difference was observed in the frequency of A1762T/G1764A dual mutations in cirrhotic HCC versus non-cirrhotic HCC patients (OR = 2.06, P = 0.05). Chronic HBV-infected patients and HCC patients with genotype B had a significantly lower risk of A1762T/G1764A dual mutations compared with patients with genotype C (OR = 0.30, P < 0.0001 and OR = 0.34, P = 0.04, respectively). In HBV genotype C subjects, A1762T/G1764A dual mutations contributed to significantly higher risk for HCC developing compared with non-mutation ones (OR = 3.47, P < 0.00001). In conclusion, A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma, particularly in an HBV genotype C population, even without progression to cirrhosis.

Combination of sorafenib and gadolinium chloride (GdCl3) attenuates dimethylnitrosamine(DMN)-induced liver fibrosis in rats.

BACKGROUND/AIMS: Liver sinusoidal endothelial cells (SECs), hepatic stellate cells (HSCs) and Kupffer cells (KCs) are involved in the development of liver fibrosis and represent a potential therapeutic target. The therapeutic effects on liver fibrosis of sorafenib, a multiple tyrosine kinase inhibitor, and gadolinium chloride (GdCl3), which depletes KCs, were evaluated in rats. METHODS: Liver fibrosis was induced in rats with dimethylnitrosamine, and the effects of sorafenib and/or GdCl3 in these rats were monitored. Interactions among ECs, HSCs and KCs were assessed by laser confocal microscopy. RESULTS: The combination of sorafenib and GdCl3, but not each agent alone, attenuated liver fibrosis and significantly reduced liver function and hydroxyproline (Hyp). Sorafenib significantly inhibited the expression of angiogenesis-associated cell markers and cytokines, including CD31, von Willebrand factor (vWF), and vascular endothelial growth factor, whereas GdCl3 suppressed macrophage-related cell markers and cytokines, including CD68, tumor necrosis factor-α, interleukin-1ß, and CCL2. Laser confocal microscopy showed that sorafenib inhibited vWF expression and GdCl3 reduced CD68 staining. Sorafenib plus GdCl3 suppressed the interactions of HSCs, ECs and KCs. CONCLUSION: Sorafenib plus GdCl3 can suppress collagen accumulation, suggesting that this combination may be a potential therapeutic strategy in the treatment of liver fibrosis.

Aspartate aminotransferase-lymphocyte ratio index and systemic immune-inflammation index predict overall survival in HBV-related hepatocellular carcinoma patients after transcatheter arterial chemoembolization.

It has been suggested that lymphocytes play central roles in host antitumor immune responses and control cancer outcome. We reviewed the clinical parameters of 189 hepatocellular carcinoma (HCC) patients and investigated the prognostic significance of lymphocyte-related scores in HCC patients following transcatheter arterial chemoembolization (TACE). Survival analysis revealed that an elevated aspartate aminotransferase-lymphocyte ratio index (ALRI) > 57 and a systemic immune-inflammation index (SII) > 300 were negatively associated with overall survival in HBV-related HCC (HR = 2.181, P = 0.003 and HR = 2.453, P = 0.003; respectively). Spearman chi-square analysis showed that ALRI had a specificity of 82.4% and that SII index had a sensitivity of 71.9% for HCC overall survival. ALRI and SII had negative predictive values of 74.6% and 80%, respectively for HCC overall survival. Additionally, Barcelona Clinic Liver Cancer (BCLC) stage C patients had significantly higher ALRI and SII scores (both P < 0.0001) and poorer overall survival (HR = 3.618, P < 0.001). Additionally, HCC patients with portal vein tumor thrombosis (PVTT) had higher ALRI and SII scores (P < 0.0001 and P = 0.0059, respectively). In conclusion, as noninvasive, low cost, easily assessable and reproducible parameters, elevated ALRI and SII should be used as negative predictive factors for overall survival in HBV-related HCC in clinical practice.

Elevation of serum GGT and LDH levels, together with higher BCLC staging are associated with poor overall survival from hepatocellular carcinoma: a retrospective analysis.

Serum biomarkers predicting prognosis have not been adequately explored in HCC patients. The aim of this study was to investigate prognostic significance of parameters of liver function, tumor markers, and other clinicopathological features in HCC patients. Medical records of HCC patients were retrospectively extracted and overall survival was evaluated with the Kaplan-Meier method. Significant difference was estimated with the Log rank method. Univariate and multivariate analyses were used for the study of significance of prognostic factor. A total of 273 HCC patients were included in this analysis. According to the Cox regression analysis and Kaplan-Meier event analysis, GGT and LDH levels of liver function tests were significantly associated with HCC overall survival. Elevated serum CEA level was a risk factor related to poor HCC overall survival. And advanced BCLC staging contributed to a lower overall survival in HCC patients. HCC could benefit from surgical resection, TACE, and radiotherapy. ROC curves demonstrated that different from CEA, elevated GGT and LDH could accurately predict HCC overall survival. In conclusion, serum GGT and LDH together with higher BCLC staging should be potential predictive factors for HCC overall survival.

HULC and H19 Played Different Roles in Overall and Disease-Free Survival from Hepatocellular Carcinoma after Curative Hepatectomy: A Preliminary Analysis from Gene Expression Omnibus.

OBJECTIVE: This study aimed to evaluate the relationships between long noncoding RNAs (lncRNAs) in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and survival. METHODS: We correlated the lncRNAs in tumor tissues with HCC survival and clinicopathological features based on Gene Expression Omnibus expression profile GSE36376. RESULTS: Eight lncRNAs and 240 HCC patients were included. Cox regression analysis indicated that HULC was a positive factor for HCC overall survival (HR = 0.885, 95% CI = 0.797-0.983, and P = 0.023) and disease-free survival time (HR = 0.913, 95% CI = 0.835-0.998, and P = 0.045). H19 and UCA1 were both demonstrated to be risk factors of HCC disease-free survival in multivariate Cox model (HR = 1.071, 95% CI = 1.01-1.137, and P = 0.022 and HR = 2.4, 95% CI = 1.092-5.273, and P = 0.029, resp.). But Kaplan-Meier method showed no significant association between UCA1 and HCC disease-free survival (log rank P = 0.616). Logistic regression demonstrated that H19 was overexpressed in HBV-infected patients (OR = 1.14, 95% CI = 1.008-1.29, and P = 0.037). HULC had a significant association with vascular invasion (OR = 0.648, 95% CI = 0.523-0.803, and P < 0.001). H19 and MEG3 were both considered to be risk factors for high AFP level (OR = 1.45, 95% CI = 1.277-1.646, and P < 0.001 and OR = 1.613, 95% CI = 1.1-2.365, and P = 0.014, resp.). CONCLUSIONS: Contributing to decreased susceptibility to vascular invasion, upregulation of HULC in tumor tissues was positively associated with HCC survival. In contrast, H19 overexpression might be risk factor for HCC aggressiveness and poor outcomes.

Correlation of APOBEC3 in tumor tissues with clinico-pathological features and survival from hepatocellular carcinoma after curative hepatectomy.

OBJECTIVE: This study aimed to evaluate the relationships between members of APOBEC3 in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and prognosis. METHODS: Using the expression profile GSE36376 from Gene Expression Omnibus (GEO), we compared APOBEC3 expression between tumor and non-tumor tissues, and correlated this with clinico-pathological features and outcomes of HCC patients. RESULTS: A3B, A3D, A3F and A3H were overexpressed in HCC tumor tissues compared to non-tumor tissues (all P≤0.001). Cox regression shown that A3G was negatively associated with overall survival of HCC patients (HR=2.277, 95% CI=1.324-3.915, P=0.033), in contrast, A3C level in tumor tissues might play a positive role in HCC overall survival (HR=0.364, 95% CI=0.182-0.727, P=0.004). Interestingly, A3F contributed to a poor disease-free survival of HCC (HR=3.383, 95% CI=1.249-9.715, P=0.017), while A3H may be a positive factor associated with HCC disease-free survival (HR=0.25, 95% CI=0.098-0.636, P=0.004). Cirrhosis, tumor size and intrahepatic metastasis were associated with HCC poor disease-free survival (HR=1.838, 95% CI=1.308-2.583, P<0.001; HR= 1.095, 95% CI=1.042-1.15, P<0.001 and HR=3.669, 95% CI=2.447-5.5, P<0.001; respectively). Logistic regression analysis indicated that up-regulation of A3F in tumor tissues promoted HCC vascular invasion, intrahepatic metastasis and AFP elevation (all P<0.05). In contrast, A3H might decrease these risks (all P<0.05). CONCLUSIONS: APOBEC3G and APOBEC3F might be risk factors for HCC development and survival, while APOBEC3C and APOBEC3H should play positive roles in HCC aggressiveness and prognosis. Further investigation for APOBEC3 mechanisms are needed in the future.

Overexpression of APOBEC3F in tumor tissues is potentially predictive for poor recurrence-free survival from HBV-related hepatocellular carcinoma.

UNLABELLED: The relationship between members of APOBEC3 in tumor tissues and hepatocellular carcinoma prognosis was not well studied. We compared APOBEC3 expression between tumor and non-tumor tissues based on the expression profile GSE14520 from Gene Expression Omnibus (GEO), and correlated APOBEC3 in tumor tissues with outcomes of HCC patients. APOBEC3B, which was significantly up-regulated in HCC tumor tissues (P < 0.001), was negatively associated with HCC overall survival by Cox regression (HR = 1.005, 95% CI = 1.0-1.009, P = 0.033). However, no significant difference was found of APOBEC3B and HCC overall survival by Kaplan-Meier method. HCC patients with high APOBEC3F expression in tumor tissues more likely coexist with multinodular tumors than those with low APOBEC3F level (26.4% and 13.6%, respectively, P = 0.018). Cox univariate and multivariate regression analyses revealed that APOBEC3F overexpression in tumor tissues was negatively associated with HCC recurrence (HR = 1.132, 95% CI = 1.013-1.265, P = 0.028). Additionally, the higher the APOBEC3F expressed, the greater risk of poor recurrence-free survival for HCC patients (mean survival time high = 32.25 and low = 42.68 months, respectively; log rank P = 0.012) when grouped by lower quartile cut-off of 10.98. CONCLUSIONS: Overexpression of APOBEC3F in tumor tissues is potentially predictive for poor recurrence-free survival from HBV-HCC patients. The role of other APOBEC3 members in HCC development needed further research.