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Validation of modified fibrosis-4 index for predicting hepatocellular carcinoma in patients with compensated alcoholic liver cirrhosis.

ABSTRACT: Recently, modified fibrosis-4 index (mFIB-4) and the easy liver fibrosis test (eLIFT) were developed for predicting liver fibrosis in chronic liver disease patients. We evaluated whether the 2 tests can predict hepatocellular carcinoma (HCC) risk in alcoholic liver cirrhosis (ALC) patients.A retrospective cohort of 924 ALC patients was assessed for HCC development. Four non-invasive serum biomarkers, mFIB-4, the eLIFT score, fibrosis-4 index (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) were tested using time-dependent analysis of areas under receiver operating characteristic curve (AUROC), DeLong, and log-rank tests.During a median 4.8 years of follow-up, HCC occurred in 83 patients (9.0%). For predicting HCC development at 3 years, the mFIB-4 showed a significantly higher AUROC than APRI and eLIFT scores (0.71 vs 0.61 and 0.56, respectively, all P?4) (P?

SUBMITTER: Kim JH

PROVIDER: S-EPMC6283079 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Validation of modified fibrosis-4 index for predicting hepatocellular carcinoma in patients with compensated alcoholic liver cirrhosis.

Kim Ji Hyun JH Lee Minjong M Park Seung Woo SW Kang Myungho M Kim Minjeong M Lee Sang Hoon SH Kim Tae Suk TS Park Jin Myung JM Choi Dae Hee DH

Medicine 20181101 48

Recently, modified fibrosis-4 index (mFIB-4) and the easy liver fibrosis test (eLIFT) were developed for predicting liver fibrosis in chronic liver disease patients. We evaluated whether the 2 tests can predict hepatocellular carcinoma (HCC) risk in alcoholic liver cirrhosis (ALC) patients.A retrospective cohort of 924 ALC patients was assessed for HCC development. Four non-invasive serum biomarkers, mFIB-4, the eLIFT score, fibrosis-4 index (FIB-4), and aspartate aminotransferase to platelet ra ...[more]

PMID: 30508959

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Project description:Background: Most hepatocellular carcinoma (HCC) patients have undergone a progression from chronic hepatitis, then liver cirrhosis (LC), and finally to carcinoma. The objective of this study was to elucidate risk factors to predict HCC development for cirrhosis patients. Methods: Multiple methylated specific PCR (MSP) was applied to determine methylation status of heparocarcinogenesis-related genes in 396 tissue and plasma specimens and multivariate cox model was used to analyze the relationship between risk variables and HCC development among cirrhosis patients, followed up in a median period of 30 months. Results: Among 105 LC cases, HCC incidence rate at 30 months was 30.48% (32/105), which were statistically associated with patients' age and aberrant methylation of p16, SFRP, and LINE1 (p<0.05). Receiver operating characteristic (ROC) curve showed the overall predictive accuracy reached the highest (90.7%) if the four risk variables were concurrent to predict HCC development. Moreover, along with the growth of age from 0-40, 40-55, to 55-70 years or the increased number of aberrantly-methylated gene from 0-1 to 2-3, the HCC incidence rate of cirrhosis patients rised from 10.00%, 12.28% to 82.14% and 17.44% to 89.47%, separately. Thus, based on combined analysis with diverse age and number of aberrantly-methylated gene, 105 cases were divided into five groups and computed their respective HCC incidecne rate to categorize them into different risk groups. Of note, A significant lifting of HCC incidence rate in the high-risk group (40-55 years coupled with 2-3 aberrantly-methylated genes, 55-70 years coupled with 0-1 aberrantly-methylated gene, 55-70 years coupled with 2-3 aberrantly-methylated genes; n=33) was observed compared with the low-risk group (0-40 years coupled with 0-1 aberrantly-methylated gene, 40-55 years coupled with 0-1 aberrantly-methylated gene; (n=72) (p<0.01). Conclusions: Ultimately, high-risk cirrhosis patients with 55-over years or 2-3 aberrantly-methylated genes should be paid more attention to be regularly screened with HCC development.

Project description:Oxidative stress is a significant contributing factor in the pathogenesis of alcoholic liver disease (ALD). In the murine models of chronic alcohol consumption, induction of oxidative stress results in increased peroxidation of polyunsaturated fatty acids to form highly reactive electrophilic ?/? unsaturated aldehydes that post-translationally modify proteins altering activity. Data are presented here suggesting that oxidative stress and the resulting carbonylation of hepatic proteins is an ongoing process involved in alcohol-induced cirrhosis.Using age-matched pooled hepatic tissue obtained from healthy humans and patients with end stage cirrhotic ALD, overall carbonylation was assessed by immunohistochemistry and LC-MS/MS of streptavidin purified hepatic whole cell extracts treated with biotin hydrazide. Identified carbonylated proteins were further evaluated using bioinformatics analyses.Using immunohistochemistry and Western blotting, protein carbonylation was increased in end stage ALD occurring primarily in hepatocytes. Mass spectrometric analysis revealed a total of 1224 carbonylated proteins in normal hepatic and end-stage alcoholic cirrhosis tissue. Of these, 411 were unique to cirrhotic ALD, 261 unique to normal hepatic tissue and 552 common to both groups. Bioinformatic pathway analysis of hepatic carbonylated proteins revealed a propensity of long term EtOH consumption to increase post-translational carbonylation of proteins involved in glutathione homeostatic, glycolytic and cytoskeletal pathways. Western analysis revealed increased expression of GSTA4 and GST? in human ALD. Using LC-MS/MS analysis, a nonenaldehyde post-translational modification was identified on Lysine 235 of the cytoskeletal protein vimentin in whole cell extracts prepared from human end stage ALD hepatic tissue.These studies are the first to use LC-MS/MS analysis of carbonylated proteins in human ALD and begin exploring possible mechanistic links with end-stage alcoholic cirrhosis and oxidative stress.

Dataset Information

Validation of modified fibrosis-4 index for predicting hepatocellular carcinoma in patients with compensated alcoholic liver cirrhosis.

Publications

Validation of modified fibrosis-4 index for predicting hepatocellular carcinoma in patients with compensated alcoholic liver cirrhosis.

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