Shear wave elastography predicts hepatocellular carcinoma risk in hepatitis C patients after sustained virological response.
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ABSTRACT:
SUBMITTER: Hamada K
PROVIDER: S-EPMC5909618 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Shear wave elastography predicts hepatocellular carcinoma risk in hepatitis C patients after sustained virological response.
Hamada Koichi K Saitoh Satoshi S Nishino Noriyuki N Fukushima Daizo D Horikawa Yoshinori Y Nishida Shinya S Honda Michitaka M
PloS one 20180419 4
<h4>Aim</h4>To evaluate the relationship between fibrosis and HCC after sustained virological response (SVR) to treatment for chronic hepatitis C (HCV).<h4>Methods</h4>This single-center study retrospectively evaluated 196 patients who achieved SVR after HCV infection. The associations of risk factors with HCC development after HCV eradication were evaluated using univariate and multivariate Cox proportional hazards regression models.<h4>Results</h4>Among the 196 patients, 8 patients (4.1%) deve ...[more]
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Project description:UnlabelledThe long-term prognosis in terms of risk or predictors of developing hepatocellular carcinoma (HCC) among patients with sustained virological response (SVR) remains unclear. We conducted a retrospective cohort study using data from the Veterans Affairs VA hepatitis C virus (HCV) Clinical Case Registry in patients with positive HCV RNA between October 1999 and August 2009 and follow-up through December 2010. HCV treatment (interferon with or without ribavirin) and SVR (RNA test negative at least 12 weeks after the end of treatment) were determined. We used Cox's proportional hazards models to calculate hazard ratios (HRs) for potential predictors (demographic, virological, and clinical) associated with HCC development post-SVR. We identified 33,005 HCV-infected individuals who received treatment, of whom 10,817 achieved SVR. Among these patients, 100 developed new HCC during a total follow-up of 30,562 person-years for an overall incidence rate of 0.33% per year. Annual risk of HCC remained considerably high among patients with cirrhosis (1.39%) and those cured after age 64 (0.95%). Patients with diabetes (adjusted HR = 1.88; 1.21-2.91) or genotype 3 infection (adjusted HR = 1.62; 0.96-2.734) were significantly more likely to develop HCC.ConclusionsRisk of HCC after HCV cure, though considerably reduced, remains relatively high at 0.33% per year. Older age and/or presence of cirrhosis at the time of SVR are associated with a high enough risk to warrant surveillance. Diabetes is also a risk factor for post-SVR HCC. (Hepatology 2016;64:130-137).
| S-EPMC4917456 | biostudies-literature
Project description:BackgroundTwo-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.MethodsWe 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.ResultsThe 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 pre-post treatment were characterized by similar prognostic abilities as high levels of these parameters. Post-treatment 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).ConclusionsThe 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.
| S-EPMC8640914 | biostudies-literature
Project description:ObjectiveLiver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients.DesignThis international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation.ResultsAfter screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM.ConclusionThe M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.
| S-EPMC8761995 | biostudies-literature
Project description:Purpose:To evaluate the prognostic value of liver stiffness (LS) measured using two-dimensional (2D) shear-wave elastography (SWE) in patients with hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA). Methods:The Institutional Review Board approved this retrospective study and informed consent was obtained from all patients. A total of 134 patients with up to 3 HCCs ?5 cm who had undergone pre-procedural 2D-SWE prior to RFA treatment between January 2012 and December 2013 were enrolled. LS values were measured using real-time 2D-SWE before RFA on the procedural day. After a mean follow-up of 33.8 ± 9.9 months, we analyzed the overall survival after RFA using the Kaplan-Meier method and Cox proportional hazard regression model. The optimal cutoff LS value to predict overall survival was determined using the minimal p value approach. Results:During the follow-up period, 22 patients died, and the estimated 1- and 3-year overall survival rates were 96.4 and 85.8%, respectively. LS measured by 2D-SWE was found to be a significant predictive factor for overall survival after RFA of HCCs, as was the presence of extrahepatic metastases. As for the optimal cutoff LS value for the prediction of overall survival, it was determined to be 13.3 kPa. In our study, 71 patients had LS values ?13.3 kPa, and the estimated 3-year overall survival was 76.8% compared to 96.3% in 63 patients with LS values <13.3 kPa. This difference was statistically significant (hazard ratio = 4.30 [1.26-14.7]; p = 0.020). Conclusion:LS values measured by 2D-SWE was a significant predictive factor for overall survival after RFA for HCC.
| S-EPMC5892360 | biostudies-literature
Project description:The introduction of a direct-acting antiviral (DAA) for patients with hepatitis C virus (HCV) infection, could lead to higher sustained virologic response (SVR) rates with fewer adverse events, and it could shorten the treatment duration relative to the interferon era. Although most recent clinical studies have demonstrated that the occurrence rates of hepatocellular carcinoma (HCC) are decreased by SVR with both interferon-based and interferon-free-regimens, there are several reports about the unexpected observation of high rates of early tumor occurrence and recurrence in patients with HCV-related HCC undergoing interferon-free therapy despite SVR. Several mechanisms of HCC occurrence and rapid immunological changes, including cytokines and chemokines during and after DAA treatment, have also been reported. We focused on the possibilities that HCC occurs or recurs during and after DAA treatment, based on the reported clinical and basic studies. Further studies and observations will be needed to determine the short-term and long-term effects on hepatocarcinogenesis caused by the eradication of HCV with DAAs. New serum biomarkers and a follow-up system for HCV-patients with SVR should be established.
| S-EPMC6323517 | biostudies-literature
Project description:Background and aimThe risk of hepatocellular carcinoma (HCC) persists in a condition of sustained virologic response (SVR) after hepatitis C virus (HCV) eradication. Comprehensive molecular analyses were performed to test the hypothesis that epigenetic abnormalities present after an SVR play a role in hepatocarcinogenesis.MethodsWhole-genome methylome and RNA sequencing were performed on HCV, SVR, and healthy liver tissue. Integrated analysis of the sequencing data focused on expression changes in transcription factors and their target genes, commonly found in HCV and SVR. Identified expression changes were validated in demethylated cultured HCC cell lines and an independent validation cohort.ResultsThe coincidence rates of the differentially methylated regions between the HCV and SVR groups were 91% in the hypomethylated and 71% in the hypermethylated regions in tumorous tissues, and 37% in the hypomethylated and 36% in the hypermethylated regions in non-tumorous tissues. These results indicate that many epigenomic abnormalities persist even after an SVR was achieved. Integrated analysis identified 61 transcription factors and 379 other genes that had methylation abnormalities and gene expression changes in both groups. Validation cohort specified gene expression changes for 14 genes, and gene ontology pathway analysis revealed apoptotic signaling and inflammatory response were associated with these genes.ConclusionThis study demonstrates that DNA methylation abnormalities, retained after HCV eradication, affect the expression of transcription factors and their target genes. These findings suggest that DNA methylation in SVR patients may be functionally important in carcinogenesis, and could serve as biomarkers to predict HCC occurrence.
| S-EPMC9730721 | biostudies-literature
Project description:IntroductionThe genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct-acting antivirals (DAA) or interferon (IFN) are still not fully understood.MethodsSixty-nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole-exome sequencing.ResultsAmong the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV-positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV-SVR. According to the HCV treatment, 35 HCV-SVR HCCs were classified into two groups: eight tumors with DAA (HCV-SVR-DAA) and 24 tumors with interferon (HCV-SVR-IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV-SVR than in HCV-positive tumors (p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV-SVR samples than in HCV-positive samples (p = 0.048). Among the patients with HCV-SVR, the frequency of samples with TP53 mutations was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors (p = 0.030). TP53 inactivation scores in HCV-SVR-DAA tumors were found to be significantly enhanced in comparison to HCV-SVR-IFN tumors (p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV-SVR-DAA tumors. HCV-SVR-DAA was significantly associated with portal vein invasion (p = 0.003) in comparison to HCV-SVR-IFN.ConclusionOur dataset potentially serves as a fundamental resource for the genomic characteristics of HCV-SVR-DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV-positive tumors and HCV-SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors.
| S-EPMC9041076 | biostudies-literature
Project description:BackgroundPatients with decompensated hepatitis C virus (HCV) cirrhosis experience various outcomes after sustained virological response (SVR), ranging from clinical recovery to further deterioration. We hypothesised that the genetic risk for steatosis, namely the polymorphisms rs738409 of Patatin-like Phospholipase Domain-Containing 3 (PNPLA3), rs58542926 of Transmembrane-6-Superfamily-2 (TM6SF2), and rs641738 of Membrane-bound O-acyltransferase Domain-Containing 7 (MBOAT7), is predictive of recovery.MethodsWe prospectively enrolled 56 patients with Child-Pugh (CPT) B/C cirrhosis who underwent antiviral therapy. The primary outcome was change in CPT score at 12, 24, and 48 weeks after SVR. We used a linear mixed-effects model for analysis.ResultsForty-five patients (PNPLA3: 21 CC, 19 CG, 5 GG) survived to the first endpoint without liver transplantation. The mean change in CPT score at 12, 24, and 48 weeks was -1.57 (SE=0.30), -1.76 (SE=0.32), and -2.0 (SE=0.36), respectively, among the patients with the PNPLA3 CC genotype and -0.50 (SE=0.20), -0.41 (SE=0.25), and -0.24 (SE=0.27), respectively, among the other 24 patients. After adjustment for baseline characteristics, the PNPLA3 CG/GG genotypes were associated with a 1.29 (SE=0.30, p<0.0001) point higher CPT score. Most of the difference came from differences in hepatic encephalopathy and bilirubin. The results for rs58542926 and rs641738 were not significant.ConclusionThe PNPLA3 CG/GG genotypes could identify a subgroup of patients with decompensated HCV cirrhosis that had suboptimal clinical recovery despite SVR. An understanding of the genetic factors that influence clinical outcomes will help target patients for liver transplant based on individual genetic risk factors and provide insight leading to new therapeutic approaches.
| S-EPMC6441264 | biostudies-literature
Project description:BackgroundTo explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection.MethodsA total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS.ResultsPathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction.ConclusionsStiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC.Clinical relevance statementTumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment.Key points• Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77.
| S-EPMC10495298 | biostudies-literature
Project description:Objectives:The aim of the study was to compare elastographic means in parathyroid adenomas, using shear wave elastography and strain elastography. Methods:This prospective study examined 20 consecutive patients diagnosed with primary hyperparathyroidism and parathyroid adenoma, confirmed by biochemical assay, technetium-99 sestamibi scintigraphy, and pathology report, after parathyroid surgery. All patients were examined on conventional 2B ultrasound, 2D shear wave elastography, and strain elastography. We determined using 2D shear wave elastography (SWE) the elasticity index (EI) in parathyroid adenoma, thyroid parenchyma, and surrounding muscle and examined using strain elastography the parathyroid adenoma, and determined the strain ratio with the thyroid tissue and muscle tissue. Results:All patients had positive sestamibi scintigraphy and underwent surgery, with confirmation of parathyroid adenoma in all cases. The mean parathormone (PTH) value before surgery was 153.29?pg/ml (36.5, 464.8) and serum calcium concentration was 10.5?mg/dl (9, 11.5). We compared using 2D-SWE and strain elastography parathyroid adenoma with thyroid tissue and with surrounding muscle. The mean EI measured by SWE in parathyroid adenoma was 4.74?±?2.74?kPa and in thyroid parenchyma was 11.718?±?4.206?kPa (mean difference?=?6.978?kPa, p < 0.001), and the mean EI value in muscle tissue was 16.362?±?3.829?kPa (mean difference?=?11.622, p < 0.001). Using ROC analysis, we found that an EI below 7?kPa correctly identifies parathyroid tissue. We evaluated parathyroid adenomas using strain elastography by color mapping and strain ratio as a semiquantitative measurement; however, we could not find any statistical correlation comparing the strain ratio obtained from the parathyroid adenoma with the thyroid tissue (p=0.485). Conclusion:Ultrasound elastography is a helpful tool in identifying parathyroid adenomas. A cutoff value below 7?kPa can be used in 2D-SWE. Color maps in strain elastography without adding strain ratio can be used, parathyroid adenoma being identified as score 1 in the Rago criteria.
| S-EPMC7103049 | biostudies-literature