How intrahepatic cholestasis affects liver stiffness in patients with chronic hepatitis B: a study of 1197 patients with liver biopsy

H, Guo; Liao, Mei; Jin, Jieyang; Zeng, Jie; Li, Shuoyang; Schroeder, Darrell R.; Zheng, Jian; Zheng, Rongqin; Chen, Shigao

doi:10.1007/s00330-019-06451-x

Cited by 27 publications

(13 citation statements)

References 29 publications

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“…Second, intrahepatic cholestasis such as jaundice and elevated bilirubin, which are common in liver decompensated cirrhosis has been identified as another factor influencing LSMs by 2D-SWE. For patients with the same F4 stage according to the Metavir fibrosis scoring system, CHB patients with abnormal bilirubin levels had higher LSMs and elevated bilirubin levels had a positive correlation with LSMs (correlation coefficient of 0.435) (19). Antiviral therapy may also decrease LSMs by improving bilirubin levels.…”

Section: Discussionmentioning

confidence: 98%

Dynamic monitoring with shear wave elastography predicts outcomes of chronic hepatitis B patients with decompensated cirrhosis

Ye¹,

Huang²,

Sun³

et al. 2021

Ann Transl Med

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Background: Two-dimensional shear wave elastography (2D-SWE) can be used to accurately assess significant liver fibrosis in chronic hepatitis B (CHB). However, whether those with decompensated cirrhosis could benefit from surveillance with 2D-SWE remains unclear. We aimed to evaluate the association between dynamic changes in 2D-SWE measurements and the prognosis of CHB-related decompensated cirrhosis.Methods: We prospectively enrolled 149 consecutive treatment-naive CHB patients with decompensated cirrhosis from a clinical trial (registration number: ChiCTR-DCD-15006000) from February 2015 to December 2018. 2D-SWE was performed at 48-week intervals until December 2020. Liver-related events (LREs) were recorded through electronic medical records and telephone interviews. Results:The liver stiffness measurement (LSM) levels persistently reduced after antiviral therapy in patients who did not develop LREs, while patients with LREs showed a fluctuating trend of LSM alterations.Low pre-treatment 2D-SWE LSM, ∆% 2D-SWE LSM pre-virus control, and ∆% 2D-SWE LSM prepost treatment were characterized by similar prognostic abilities as high levels of these parameters. Posttreatment 2D-SWE LSM was independently correlated with LREs in multivariate Cox regression models after antiviral treatments [hazard ratio (HR) =1.05; 95% confidence interval (CI): 1.02-1.08, P=0.0007 and 1.11; 95% CI: 1.04-1.18, P=0.0026]. Receiver operating characteristic (ROC) curve analysis identified that post-treatment 2D-SWE LSM exhibited the best predictive power for LREs among all the other variables, including parameters of 2D-SWE and serum fibrosis markers (area under the curve =0.75, P<0.001). Conclusions:The last follow-up LSM, rather than pre-treatment or dynamic changes in 2D-SWE serves as a powerful predictor of LREs, suggesting that sequential monitoring may be beneficial to predicting prognosis.

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Section: Discussionmentioning

confidence: 98%

Dynamic monitoring with shear wave elastography predicts outcomes of chronic hepatitis B patients with decompensated cirrhosis

Ye¹,

Huang²,

Sun³

et al. 2021

Ann Transl Med

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“…We demonstrated that a baseline tumor LS of >19.53 kPa was associated with higher rates of PD. We chose to test tumor LS values measured by SWE as a potential tool for predicting treatment efficacy of PD-1 inhibitor-based therapy for the following reasons: 1) with recent advances in ultrasound technology, various elastography techniques, including TE and SWE, have been confirmed to be effective tools for staging the degree of fibrosis ( 15 – 17 ); 2) in contrast to TE, SWE provides additional real-time information on tumorous foci, enabling a more detailed characterization that can help to predict the nature and behavior of the tumor ( 35 ); and 3) compared to TE, SWE shows a higher rate of reliable measurements and a similar predictive value for fibrosis, as determined in a meta-analysis of 13 studies ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

“…With recent advances in ultrasound technology, various elastography techniques have been found to be effective in staging liver fibrosis, among which shear wave elastography (SWE)—which uses the supersonic shear imaging technique—is capable of predicting overall survival in patients after radiofrequency ablation for HCC ( 14 ). In addition, previous studies reported that liver stiffness (LS) values measured by SWE achieved better sensitivity and specificity than those measured by transient elastography (TE), the aspartate aminotransferase (AST) to Platelet Ratio Index, or the Fibrosis 4 score in patients with chronic hepatitis B ( 15 – 17 ). However, the clinical implications of baseline LS values by SWE in patients with advanced HCC who are treated with anti-PD-1/PD-L1 or in those treated with anti-PD-1/PD-L1 in combination with an antiangiogenic regimen have not been explored.…”

Section: Introductionmentioning

confidence: 99%

Hepatic Tumor Stiffness Measured by Shear Wave Elastography Is Prognostic for HCC Progression Following Treatment With Anti-PD-1 Antibodies Plus Lenvatinib: A Retrospective Analysis of Two Independent Cohorts

et al. 2022

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BackgroundThe clinical significance of liver stiffness (LS) measured by shear wave elastography (SWE) in programmed cell death protein-1 (PD-1) inhibitors treated advanced hepatocellular carcinoma (HCC) patients remains unknown. This study aimed to explore the prognostic value of baseline LS by SWE prior to PD-1 inhibitor treatment in combination with lenvatinib.MethodsWe retrospectively evaluated patients (n=133) with HCC who received anti-PD-1 antibodies plus lenvatinib at two high-volume medical centres, between January 2020 and June 2021. Univariate and multivariate logistic regression analysis were used to develop a novel nomogram. RNA sequencing and immunohistochemical staining were used to assess the heterogeneity of biological and immune characteristics associated with tumor stiffness.ResultsThe objective response rate (ORR) and disease control rate (DCR) of the whole population were 23.4% and 72.2%, respectively. A LS value of the baseline tumorous foci of 19.53 kPa had the maximum sum of sensitivity and specificity, making it the optimal cut-off value for predicting PD-1 inhibitor efficacy. The nomogram comprised baseline tumor LS and albumin-bilirubin grade (ALBI), which provided favorable calibration and discrimination in the training dataset with an AUC of 0.840 (95%CI: 0.750-0.931) and a C-index of 0.828. Further, it showed acceptable discrimination in the validation cohort, with an AUC of 0.827 (95%CI: 0.673-0.980) and C-index of 0.803. The differentially expressed genes enriched in high stiffness tumors were predominantly associated with metabolic pathways, while those enriched in low stiffness tumors were related to DNA damage repair. Furthermore, patients with high stiffness tumors had a relatively lower infiltration of immune cells and histone deacetylase pathway inhibitors were identified as candidate drugs to promote the efficacy of immunotherapy.ConclusionsBaseline LS value of tumorous foci by SWE—that is, before administration of a PD-1 inhibitor in combination with lenvatinib—is a convenient predictor of PD-1 inhibitor efficacy in patients with advanced HCC, which has potential to be used for pretreatment stratification to optimize treatment of advanced HCC.

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“…Evidence suggests that CHB patients predispose towards other hepatic comorbidities ( Liu et al, 2018 ; Oh et al, 2020 ), in addition to viral factors, in which immune, inflammatory, and metabolic disorders also have pivotal roles ( Seto et al, 2018 ). Meanwhile, these chronic liver diseases (CLDs) can in turn affect the disease progression ( Yu et al, 2017 ; Choi et al, 2020 ; Guo et al, 2020 ; Bockmann et al, 2021 ) and the efficacy of antiviral strategies in CHB patients ( Jin et al, 2012 ; Kim et al, 2019 ). Consequently, we hypothesized that TDF can inhibit the replication of HBV (a major cause of CLDs) and also attenuate CLDs directly by regulating the hepatic immune, inflammatory, and metabolic status of the host.…”

Section: Discussionmentioning

confidence: 99%

Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model

Duan

Chen

et al. 2021

Front. Mol. Biosci.

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Accumulating evidence suggests that tenofovir disoproxil fumarate (TDF) can attenuate liver fibrosis directly, the mechanism of which, however, has not been fully elucidated, and there is a paucity of data concerning whether TDF can also mitigate other chronic liver diseases (CLDs). We aimed to identify the molecular targets and potential mechanism of TDF itself in ameliorating CLDs. RNA-sequencing was performed on mouse liver tissues treated with TDF or normal saline. Then the differentially expressed genes (DEGs) were screened, and enrichment analyses of the function and signaling pathways of DEGs were performed with Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape. Next, protein-protein interaction (PPI) networks were constructed and module analyses were utilized to identify significant genes. Subsequently, the DisGeNET platform was used to identify the potential target genes of TDF in mitigating these diseases. Finally, prediction of the transcription factors (TFs) and microRNAs (miRNAs) of the target genes was done to conjecture the underlying mechanism by which TDF relieved CLDs. As a result, a total of 854 DEGs were identified, and the DEGs were involved mainly in “immunity,” “inflammation,” and “metabolism” processes. In addition, 50 significant genes were obtained via PPI construction and module analyses. Furthermore, by means of DisGeNET, 19 genes (Adra2a, Cxcl1, Itgam, Cxcl2, Ccr1, Ccl5, Cxcl5, Fabp5, Sell, Lilr4b, Ccr2, Tlr2, Lilrb4a, Tnf, Itgb2, Lgals3, Cxcr4, Sucnr1, and Mme) were identified to be associated with nine CLDs. Finally, 34 miRNAs (especially mmu-miR-155-5p) and 12 TFs (especially Nfkb1) were predicted to be upstream of the nine target genes (Cxcl1, Cxcl2, Ccl5, Ccr2, Sell, Tlr2, Tnf, Cxcr4, and Mme) of TDF in ameliorating CLDs. In conclusion, our study suggests that TDF have the potential to ameliorate CLDs independently of its antiviral activity by affecting the expression of genes involved in hepatic immune, inflammatory, and metabolic processes via mmu-miR-155-5p-NF-κB signaling. These findings provided prima facie evidence for using TDF in CHB patients with concurrent CLDs.

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How intrahepatic cholestasis affects liver stiffness in patients with chronic hepatitis B: a study of 1197 patients with liver biopsy

Cited by 27 publications

References 29 publications

Dynamic monitoring with shear wave elastography predicts outcomes of chronic hepatitis B patients with decompensated cirrhosis

Dynamic monitoring with shear wave elastography predicts outcomes of chronic hepatitis B patients with decompensated cirrhosis

Hepatic Tumor Stiffness Measured by Shear Wave Elastography Is Prognostic for HCC Progression Following Treatment With Anti-PD-1 Antibodies Plus Lenvatinib: A Retrospective Analysis of Two Independent Cohorts

Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model

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