Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients

Liang, Kung–Hao; Zhang, Peng; Lin, Cheng‐Jui; Wang, Stewart C.; Hu, Tsung–Hui; Yeh, Chi-Ju; Su, Grace L.

doi:10.1007/s10620-019-05915-w

“…AFP is an onco-fetoprotein produced by cancer cells. A wealth of literature has shown the usefulness of AFP for indicating imminent HCC [15][16][17][18][19][20][21]. In addition to the two biomarkers (ALT and AFP) attributed to hepatitis flares, IL-17 represents a distinct immunological aspect of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Alpha-fetoprotein (AFP) is a diagnostic biomarker of HCC and one of the most studied predictive biomarkers of imminent HCC that has high specificity [15][16][17][18][19][20][21]. However, HCC can still occur in patients without prominent AFP elevation, resulting in unsatisfactory sensitivity using AFP alone [15].…”

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confidence: 99%

Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients

Liang

¹

,

Lai

²

,

Lin

³

et al. 2021

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Background Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study. Methods We investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining. Results IL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893–0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: $${\text{R}} = (2.6914)*{\text{IL-17}} + (0.3909)*{\text{AFP}} - (0.80812875)*{\text{IL-17}}^{2} + (0.10288876884)*{\text{IL-17}}^{2} *{\text{AFP}}.$$ R = ( 2.6914 ) ∗ IL-17 + ( 0.3909 ) ∗ AFP - ( 0.80812875 ) ∗ IL-17 2 + ( 0.10288876884 ) ∗ IL-17 2 ∗ AFP . Conclusions The circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year.

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“…The HCC risk models were constructed by the multivariate combination of variables using the generalized iterative modelling method (GIM). This algorithm can identify optimum polynomial combinations of variables with respect to the fitness function 18,19 , which in this research is the likelihood function as in the Cox regression. The software code of GIM (capable of doing the time-to-event analysis) can be downloaded at the following website (https ://githu b.com/khlia ng/GIM).…”

Section: Methodsmentioning

confidence: 99%

Plasma phenylalanine and glutamine concentrations correlate with subsequent hepatocellular carcinoma occurrence in liver cirrhosis patients: an exploratory study

Liang

¹

,

Cheng

²

,

Lo

³

et al. 2020

Sci Rep

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Aberrant metabolisms have been hypothesized to precede the occurrence of hepatocellular carcinoma (HCC), therefore, we investigated biomarkers associated with subsequent HCC in peripheral bloods using metabolomic technologies. A cohort of 475 HCC-naïve liver cirrhotic patients were recruited and prospectively followed. A total of 39 patients developed HCC in the follow-up period. Baseline plasma metabolites were explored using untargeted nuclear magnetic resonance. candidates were then quantified by ultra-performance liquid chromatography. A series of univairiate and multivariate analysis showed that phenylalanine (phe) and Glutamine (Gln) levels are associated with time to HCC, independent of viological etiologies and age. A HCC risk score R was then constructed using the polynomial combination of age, Phe and Gln in the units of micromolar (μM): R correlates with the time to HCC significantly (Hazard ratio [HR] = 2.368, 95% confidence interval [CI] 1.760-3.187, P < 0.001). An additional cross-sectional analysis showed that Phe and Gln concentrations both correlates with HCC occurrence in the next 3 years (area under the receiver operating characteristic curve [AUC] = 0.607 and 0.629, P = 0.033 and 0.010 respectively). In conclusion, phenylalanine and glutamine concentrations in the peripheral blood correlate with subsequent Hcc. Abbreviations HCC Hepatocellular carcinoma NMR Nuclear magnetic resonance R = Age * (0.0694) + Phe * (0.3399) + Phe 2 * (−0.00188154)

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“…After screening 1072 records, we retained 16 studies for full-text reading. Three studies were excluded because one study had an incorrect population [17], and the other two were incorrect exposures [18,19]. Three additional studies were excluded because missing data could not be obtained after asking the original authors [20][21][22].…”

Section: Resultsmentioning

confidence: 99%

Prognostic value of preoperative low bone mineral density in patients with digestive cancers: a systematic review and meta-analysis

Watanabe

¹

,

Saitsu

²

,

Miki

³

et al. 2022

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Purpose Osteopenia typically presents low bone mineral density (BMD) and has recently been reported as a prognostic factor in various cancers. However, the prognostic value of osteopenia in digestive tract cancers remains to be defined. We aimed to review the prognostic value of preoperative osteopenia in patients with digestive cancers. Methods Cohort studies evaluating the prognostic value of preoperative osteopenia in digestive cancers (colorectal, esophageal, hepatic, bile duct, and pancreatic cancer) were searched using electronic databases and trial registries. The exposure was defined as low BMD estimated by computed tomography at 11th thoracic vertebra, while comparator was normal BMD. The primary outcomes were overall survival and recurrence-free survival for osteopenia. Random effect meta-analyses were performed. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence. Results A total of 11 studies (2230 patients) were included. Osteopenia was an independent risk factor for overall survival (hazard ratio [HR] = 2.02, 95% CI = 1.47 to 2.78; I2 = 74%), along with sarcopenia. Osteopenia also predicted poor recurrence-free survival (HR = 1.96, 95% CI = 1.36 to 2.81; I2 = 85%). In subgroup analyses, osteopenia predicted prognosis in colorectal, esophageal, hepatic, and bile duct cancers, but not in pancreatic cancer. The certainty of the evidence was low due to inconsistency and publication bias. Conclusion Osteopenia may be independently associated with poor prognosis in patients with digestive tract cancer. Further studies are needed to establish the relevance of osteopenia in the operative prognosis of these patients.

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Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients

Cited by 8 publications

References 37 publications

Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients

Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients

Plasma phenylalanine and glutamine concentrations correlate with subsequent hepatocellular carcinoma occurrence in liver cirrhosis patients: an exploratory study

Prognostic value of preoperative low bone mineral density in patients with digestive cancers: a systematic review and meta-analysis

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