ALT Flare Predicts Hepatocellular Carcinoma Among Antiviral Treated Patients With Chronic Hepatitis B: A Cross-Country Cohort Study

Du, Yanan; Du, Bingying; Fang, Xiaoyan; Shu, Meng; Zhang, Yongjing; Chung, Hsingwen; Sun, Ye; Teng, Jiaming; Visalath, Phimphone; Qiu, Hong; Cai, Wei

doi:10.3389/fonc.2020.615203

Cited by 10 publications

(6 citation statements)

References 26 publications

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“…32 It also has important clinical significance in the prognosis of cancer. 33 An increase in the ALT is a predictor of HCC development; 34 previous researches demonstrated that patients with HCVassociated cirrhosis with a sustained high serum ALT level were at high risk for HCC development and those with a low ALT level were at low rate of development of HCC. [35][36] Induction of membrane lipid peroxidation by the released free radicals and stimulation of inflammation is followed by hepatic cell damage and excessive release of ALT.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid–induced hepatic pre-neoplastic lesions in rats

et al. 2021

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Hepatocellular carcinoma (HCC) accounts for more than 5% of all human cancers. Diacerein (DIA), an interleukin (IL)-1β inhibitor, is used for the treatment of osteoarthritis. DIA is a potential anticancer drug acting on several protein targets in the process of apoptosis. The present study aimed to explore the molecular mechanisms underlying the effect of DIA in the treatment of trichloroacetic acid (TCA)–induced pre-neoplastic changes in rats. Rats were allocated into 5 groups and treated for 4 weeks. Group 1: control; received vehicle, Group 2: TCA group; received TCA (1 g/kg, orally for 5 days). Group 3: DIA-treated group; received TCA +DIA (50 mg/kg/day, orally, for 4 weeks). Group 4: positive control group; received TCA (1 g/kg, orally, for 5 days) + 5-fluorouracil (5-FU) (75 mg/kg) intraperitoneally (i.p.), for 4 weeks as a standard anticancer drug. Group 5: received TCA (1 g/kg, orally for 5 days) + DIA (50 mg/kg/day, orally, for 4 weeks) + 5-FU (75 mg/kg, i.p., for 4 weeks). Serum liver enzymes, oxidative stress parameters, inflammatory parameter (IL-1β), and angiogenesis marker vascular endothelial growth factor (VEGF) were assessed along with histopathological evaluation. An apoptotic marker as caspase-3 expression was measured by western blot analysis. Immunoexpression of proliferating cell nuclear antigen (PCNA) and hypoxia-inducible factor-1α (HIF-1α) was evaluated. Results and conclusion: The outcomes proved that at histological level, DIA ameliorated hepatic precancerous lesion via modulation of IL-1β–HIF-1α–VEGF pathway. Conclusion IL-1β mediates angiogenesis indirectly, as it has been shown to induce hypoxia-inducible factor-1α (HIF-1α) which upregulates VEGF.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid–induced hepatic pre-neoplastic lesions in rats

et al. 2021

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“…Additionally, Du al. [32] observed the risk of HCC in patients with ALT elevation (1.82-2.75-fold). Individuals with chronic HBV who had chronically abnormal ALT may have been included in or referred to by the population that had high ALT.…”

Section: Discussionmentioning

confidence: 93%

Vitamin D Receptor BsmI and Vitamin D Binding Protein Polymorphisms associated with Hepatocellular Carcinoma Susceptibility in Cirrhotic HCV Patients

Elmasry

Medhat

El-Bendary

et al. 2023

Preprint

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Background: The severity of chronic hepatitis C and susceptibility to hepatocellular carcinoma (HCC) are currently associated with specific genetic variations within vitamin D receptor (VDR). This study aims to assess the association of VDR and vitamin D binding protein (DBP) gene polymorphisms with HCC susceptibility in Egyptian cirrhotic HCV patients. Methods: Single nucleotide polymorphisms (SNPs) in the VDR (rs2228570, rs3782905, rs11568820) and DBP rs7041 genes were genotyped using single-stranded polymorphism PCR (SSP-PCR) or restriction fragment length-PCR (RFLP-PCR) techniques. These SNPs genotypes, haplotypes and linkage disequilibrium analyses were examined in 299 Egyptian individuals (100 HCV-cirrhotic patients, 99 HCC- HCV patients, and 100 healthy controls). Logestic regression analysis was also applied to determine association with HCC progression risk. Result: The VDR rs2228570 CC genotype, VDR rs3782905 GC and CC genotypes, and DBP rs7041 GG genotype are significantly correlated with a higher risk of HCC. It is noteworthy that, VDR rs3782905 CC and DBP rs7041 TG genotypes are more associated with higher risk of HCV induced liver cirrhosis than with HCC progression in HCV infected patients. Furthermore, among patients, the relationship between these SNPs and smoking status, gender, and HCC susceptibility was reported. Conclusion: Among the four investigated SNPs, there is an association between VDR rs3782905 and DBP rs7041 and the HCC progression in Egyptian patients chronically infected with HCV. The combinations of these SNPs with smoking status and gender are statistically linked to a high risk of HCC. These results suggest that VDR polymorphisms may be potential determinants for HCC susceptibility in Egyptian HCV patients.

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“…It has been showed in previous studies that ALT, Age, PLT and LS were independent variables for severity of liver injury [ 25 – 27 ]. In the study, we also found that there are positive correlations between these indexes and liver injury, in agreement with the previous reports.…”

Section: Discussionmentioning

confidence: 99%

A noninvasive model discriminating significant histological changes in treatment-naive chronic hepatitis B patients with normal ALT

Teng

Visalath

et al. 2023

Virol J

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Background Traditionally part of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) are recommended to antiviral therapy referring to liver biopsy. However, liver biopsy is an invasive method with various potential complications. A noninvasive model was established in the study to evaluate liver histology and to identify the need of antiviral therapy. Methods A total of 614 liver biopsied CHB patients with ALT less than upper limit of normal from 2 centers were retrospectively analyzed. They were divided into a training cohort and a validation cohort. A noninvasive model to predict the significant liver histological changes was established and validated. Results The results of analysis showed that ALT, Age, platelet (PLT) and liver stiffness (LS) were independent risk factors for significant liver injury. The model was established based on the 4 indexes, with the area under the curve of 0.85 and 0.87 in training cohort and validation cohort. Meanwhile, 2 cut-off scores were selected. By applying the low cut-off score (− 0.207), patients without significant liver injury could be identified with high accuracy, with negative predictive value of 72.7% and 73.7% in training and validation cohorts. By applying the high cut-off score (0.537), the presence of significant liver injury could be diagnosed with high accuracy, with positive predictive value of 90.3% and 88.8% in the training and validation cohorts. By applying the model, liver biopsy would have been avoided in 87.6% (538/614) patients, with correct prediction in 87.9% (473/538). Conclusion The novel noninvasive model composed of ALT, Age, PLT, LS can correctly assess liver histology in CHB patient with normal ALT, which helps to determine the need of antiviral therapy without liver biopsy.

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ALT Flare Predicts Hepatocellular Carcinoma Among Antiviral Treated Patients With Chronic Hepatitis B: A Cross-Country Cohort Study

Cited by 10 publications

References 26 publications

Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid–induced hepatic pre-neoplastic lesions in rats

Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid–induced hepatic pre-neoplastic lesions in rats

Vitamin D Receptor BsmI and Vitamin D Binding Protein Polymorphisms associated with Hepatocellular Carcinoma Susceptibility in Cirrhotic HCV Patients

A noninvasive model discriminating significant histological changes in treatment-naive chronic hepatitis B patients with normal ALT

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