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Impact of cirrhosis on long-term survival outcomes of patients with intrahepatic cholangiocarcinoma.Cancer Medicine Oct 2022The correlation between cirrhosis and the long-term oncological outcome in intrahepatic cholangiocarcinoma (ICC) is debatable, and this study aimed to explore the impact...
BACKGROUND
The correlation between cirrhosis and the long-term oncological outcome in intrahepatic cholangiocarcinoma (ICC) is debatable, and this study aimed to explore the impact of cirrhosis on the long-term prognosis of patients with ICC.
METHODS
A total of 398 ICC patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2018. The diagnosis of cirrhosis was based on the Ishak fibrosis score provided by the SEER database. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were performed to minimize the potential confounders. Overall survival (OS) and cancer-specific survival (CSS) were observed, and the Cox regression model was used to select potential factors that affect the prognosis of the patients with ICC.
RESULTS
Of the included patients, there were 142 patients and 256 patients in the cirrhotic and noncirrhotic groups, respectively. Additionally, 299 of 398 patients (75.1%) died following a median follow-up of 19 months (interquartile range [IQR], 7, 43). The OS and CSS indicated advantage trend in the noncirrhotic group than the cirrhotic group in either the original cohort (OS: 17 vs 12 months, p = 0.023; CSS: 26 vs 15 months, p = 0.004) or the PSM (OS: 17 vs 12 months, p = 0.52; CSS: 22 vs 14 months, p = 0.15) or IPTW (OS: 20 vs 13 months, p = 0.163; CSS: 22 vs 15 months, p = 0.059) cohorts. Subgroup analyses displayed that the prognosis of patients who experienced surgery for ICC in the noncirrhotic group was better than that of the cirrhotic group with regard to OS and CSS.
CONCLUSIONS
Collectively, it seems that the noncirrhotic patients have similar relative OS but better CSS compared with that of the cirrhotic patients.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Humans; Liver Cirrhosis; Prognosis
PubMed: 35415945
DOI: 10.1002/cam4.4740 -
Journal of Clinical Medicine Oct 2022Background: Although liver biopsy remains the gold standard for the diagnosis and the monitoring of liver disease, non-invasive biomarkers have been recently suggested...
Background: Although liver biopsy remains the gold standard for the diagnosis and the monitoring of liver disease, non-invasive biomarkers have been recently suggested to predict liver disease severity, progression, and response to therapy. We investigated multiple tissue and circulating markers of angiogenesis in predicting the severity of biopsy-validated chronic liver diseases in patients with chronic hepatitis C virus (HCV) and in NAFLD/NASH patients. Methods: We studied samples from forty-six patients with HCV and/or NAFLD who underwent liver biopsy, liver ultrasonography, and liver stiffness measurement. Ishak and Brunt scores were calculated. Expression of selective genes and luminex analyses of 17 different circulating pro-angiogenic factors were performed. Results: The phenotype of NAFLD/NASH or HCV subjects was similar, except for insulin, which was expressed at higher levels in NAFLD/NASH patients. A Mann−Whitney test showed significant differences for the circulating levels of HB-EGF and for follistatin between HCV and NAFLD/NASH patients. In HCV patients, we found an inverse correlation between disease stage and BMP-9 and VEGF-A circulating levels, while in NASH/NAFLD direct correlations between stage and BMP-9 and VEGF-A circulating levels were noted. The K-means algorithm divided HCV and NASH/NAFLD patients in two clusters with significant differences between them. Logistic regression models showed a positive relationship with BMP-9 levels for NASH/NAFLD and with HB-EGF circulating concentrations for HCV. ROC analysis showed for BMP-9 > 1188 pg/mL a worse disease in NASH/NAFLD, whereas for HB-EGF < 61 pg/mL a higher severity of disease in HCV. Conclusion: Our data show that circulating biomarker profiles can identify the severity of chronic liver disease of NAFLD/NASH or HCV origin.
PubMed: 36294318
DOI: 10.3390/jcm11205985 -
Hepatology Communications Nov 2021Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease in children and may lead to cirrhosis requiring liver transplant. Thus, prompt diagnosis of...
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease in children and may lead to cirrhosis requiring liver transplant. Thus, prompt diagnosis of advanced fibrosis is essential. Our objectives were to examine PRO-C3 (a neo-epitope pro-peptide of type III collagen formation) levels across childhood/adolescence and associations with advanced fibrosis in pediatric NAFLD. This cross-sectional study included 88 children and adolescents with biopsy-proven NAFLD (mean age: 13.9 ± 2.9 years, 71% male) and 65 healthy participants (11.8 ± 4.5 years, 38% male). PRO-C3, and the bone remodeling biomarkers C-terminal telopeptide of type I collagen (CTX-I; bone resorption) and osteocalcin (N-MID; bone formation), were measured in serum by enzyme-linked immunosorbent assay. Fibrosis was assessed by liver biopsy in participants with NAFLD, who were categorized as having advanced (Ishak score ≥ 3) or none/mild fibrosis (Ishak score ≤ 2). Overall, PRO-C3 was similar in participants with NAFLD (median [interquartile range]: 20.6 [15.8, 25.9] ng/mL) versus healthy participants (19.0 [13.8, 26.0] ng/mL), but was significantly lower in older adolescents ≥ 15 years old (16.4 [13.0, 21.2] ng/mL) compared with children ≤ 10 years old (22.9 [18.1, 28.4] ng/mL; P < 0.001) or 11-14 years old (22.4 [18.3, 31.2] ng/mL; P < 0.001). PRO-C3 was also directly correlated with levels of CTX-I and N-MID (r = 0.64 and r = 0.62, respectively; both P < 0.001). Among participants with NAFLD, PRO-C3 was higher in those with advanced fibrosis (median [IQR]: 28.5 [21.6, 37.6]) compared with none/mild fibrosis (20.3 [18.2, 22.8]; P = 0.020) in models adjusted for age, sex, and body mass index z-score. However, associations were attenuated after additionally adjusting for bone-remodeling CTX-I (P = 0.09) or N-MID (P = 0.08). Conclusion: Collectively, these findings show that PRO-C3 levels are higher in children with advanced fibrosis in NAFLD, but are also influenced by age and pubertal growth spurt, assessed by bone remodeling biomarkers, and therefore may not be a reliable biomarker for liver fibrosis in pediatric NAFLD until late adolescence.
Topics: Adolescent; Age Factors; Biomarkers; Bone Remodeling; Child; Collagen Type I; Complement C3; Cross-Sectional Studies; Female; Humans; Liver Cirrhosis; Male; Non-alcoholic Fatty Liver Disease; Osteocalcin; Peptides; Puberty; Severity of Illness Index
PubMed: 34558828
DOI: 10.1002/hep4.1766 -
Sensors (Basel, Switzerland) Mar 2022In clinical practice, the Ishak Score system would be adopted to perform the evaluation of the grading and staging of hepatitis according to whether portal areas have...
In clinical practice, the Ishak Score system would be adopted to perform the evaluation of the grading and staging of hepatitis according to whether portal areas have fibrous expansion, bridging with other portal areas, or bridging with central veins. Based on these staging criteria, it is necessary to identify portal areas and central veins when performing the Ishak Score staging. The bile ducts have variant types and are very difficult to be detected under a single magnification, hence pathologists must observe bile ducts at different magnifications to obtain sufficient information. This pathologic examinations in routine clinical practice, however, would result in the labor intensive and expensive examination process. Therefore, the automatic quantitative analysis for pathologic examinations has had an increased demand and attracted significant attention recently. A multi-scale inputs of attention convolutional network is proposed in this study to simulate pathologists' examination procedure for observing bile ducts under different magnifications in liver biopsy. The proposed multi-scale attention network integrates cell-level information and adjacent structural feature information for bile duct segmentation. In addition, the attention mechanism of proposed model enables the network to focus the segmentation task on the input of high magnification, reducing the influence from low magnification input, but still helps to provide wider field of surrounding information. In comparison with existing models, including FCN, U-Net, SegNet, DeepLabv3 and DeepLabv3-plus, the experimental results demonstrated that the proposed model improved the segmentation performance on Masson bile duct segmentation task with 72.5% IOU and 84.1% F1-score.
Topics: Bile Ducts; Image Processing, Computer-Assisted; Liver; Neural Networks, Computer
PubMed: 35408293
DOI: 10.3390/s22072679 -
Radiology Jan 2013To evaluate the feasibility of using contrast material-enhanced computed tomographic (CT) measurements of hepatic fractional extracellular space (fECS) and...
PURPOSE
To evaluate the feasibility of using contrast material-enhanced computed tomographic (CT) measurements of hepatic fractional extracellular space (fECS) and macromolecular contrast material (MMCM) uptake to measure severity of liver fibrosis.
MATERIALS AND METHODS
All procedures were approved by and executed in accordance with University of California, San Francisco, institutional animal care and use committee regulations. Twenty-one rats that received intragastric CCl(4) for 0-12 weeks were imaged with respiratory-gated micro-CT by using both a conventional contrast material and a novel iodinated MMCM. Histopathologic hepatic fibrosis was graded qualitatively by using the Ishak fibrosis score and quantitatively by using morphometry of the fibrosis area. Hepatic fECS and MMCM uptake were calculated for each examination and correlated with histopathologic findings by using uni- and multivariate linear regressions.
RESULTS
Ishak fibrosis scores ranged from a baseline of 0 in untreated animals to a maximum of 5. Histopathologic liver fibrosis area increased from 0.46% to 3.5% over the same interval. Strong correlations were seen between conventional contrast-enhanced CT measurements of fECS and both the Ishak fibrosis scores (R(2) = 0.751, P < .001) and the fibrosis area (R(2) = 0.801, P < .001). Strong negative correlations were observed between uptake of MMCM in the liver and Ishak fibrosis scores (R(2) = 0.827, P < .001), as well as between uptake of MMCM in the liver and fibrosis area (R(2) = 0.643, P = .001). Multivariate linear regression analysis showed a trend toward independence for fECS and MMCM uptake in the prediction of Ishak fibrosis scores, with an R(2) value of 0.86 (P = .081 and P = .033, respectively).
CONCLUSION
Contrast-enhanced CT measurements of fECS and MMCM uptake are individually capable of being used to estimate the degree of early hepatic fibrosis in a rat model.
SUPPLEMENTAL MATERIAL
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112452/-/DC1.
Topics: Algorithms; Animals; Contrast Media; Feasibility Studies; Liver Cirrhosis; Pattern Recognition, Automated; Radiographic Image Enhancement; Radiographic Image Interpretation, Computer-Assisted; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 23169796
DOI: 10.1148/radiol.12112452 -
Frontiers in Immunology 2023Torque teno virus (TTV) replication is controlled by immune status, mirroring a degree of immunosuppression after solid organ transplantation. TTV viraemia (TTVv) was...
INTRODUCTION
Torque teno virus (TTV) replication is controlled by immune status, mirroring a degree of immunosuppression after solid organ transplantation. TTV viraemia (TTVv) was associated with acute cellular rejection and infection within the first year after liver transplantation (LT). Long-term data on TTV after LT and correlation with graft injury from protocol biopsies are limited.
METHODS
One hundred plasma samples paired with graft biopsies from a prospective single-center biorepository were analyzed.
RESULTS
The median time post-LT was 23 months (range, 2-298). TTVv was detectable in 97%. TTVv decreased over time after LT and showed a significant decline from year 1 to later time points. Hence, TTVv correlated negatively with histologic liver fibrosis (liver allograft fibrosis and Ishak scores) and positively with the overall immunosuppression degree quantified by an immunosuppression score in the first year after LT. There was no association with dosages or trough levels of single immunosuppressants. The pharmacodynamic marker TTVv did not correlate with pharmacokinetic assessments of immunosuppression degree [calcineurin inhibitor (CNI) trough levels or immunosuppressant dosages]-our clinical gold standards to guide immunosuppressive therapy. TTVv was independently associated with histologically proven liver fibrosis after LT in the first year after LT in multivariate analysis.
DISCUSSION
The independent association of histological graft fibrosis with lower TTVv in year 1 underscores that a pharmacodynamic marker would be preferable to individualize immunosuppression after LT. However, a high variability of TTVv at the low immunosuppression doses given after the first year precludes TTV as a clinically useful marker after LT in the long-term liver transplant recipients.
Topics: Humans; Liver Transplantation; Torque teno virus; Viremia; Prospective Studies; Liver Cirrhosis; Immunosuppressive Agents
PubMed: 37533865
DOI: 10.3389/fimmu.2023.1215868 -
Asian Journal of Surgery Jan 2021
Topics: Carcinoma, Hepatocellular; Disease-Free Survival; Female; Forecasting; Hepatectomy; Hepatitis B, Chronic; Humans; Liver Neoplasms; Male; Neoplasm Staging; Platelet Count; Preoperative Period; Prognosis; Propensity Score; Survival Rate; Thrombocytopenia
PubMed: 33248896
DOI: 10.1016/j.asjsur.2020.10.027 -
Heart (British Cardiac Society) Jul 2023Beta-blockers (BB) are an established treatment following myocardial infarction (MI). However, there is uncertainty as to whether BB beyond the first year of MI have a...
OBJECTIVE
Beta-blockers (BB) are an established treatment following myocardial infarction (MI). However, there is uncertainty as to whether BB beyond the first year of MI have a role in patients without heart failure or left ventricular systolic dysfunction (LVSD).
METHODS
A nationwide cohort study was conducted including 43 618 patients with MI between 2005 and 2016 in the Swedish register for coronary heart disease. Follow-up started 1 year after hospitalisation (index date). Patients with heart failure or LVSD up until the index date were excluded. Patients were allocated into two groups according to BB treatment. Primary outcome was a composite of all-cause mortality, MI, unscheduled revascularisation and hospitalisation for heart failure. Outcomes were analysed using Cox and Fine-Grey regression models after inverse propensity score weighting.
RESULTS
Overall, 34 253 (78.5%) patients received BB and 9365 (21.5%) did not at the index date 1 year following MI. The median age was 64 years and 25.5% were female. In the intention-to-treat analysis, the unadjusted rate of primary outcome was lower among patients who received versus not received BB (3.8 vs 4.9 events/100 person-years) (HR 0.76; 95% CI 0.73 to 1.04). Following inverse propensity score weighting and multivariable adjustment, the risk of the primary outcome was not different according to BB treatment (HR 0.99; 95% CI 0.93 to 1.04). Similar findings were observed when censoring for BB discontinuation or treatment switch during follow-up.
CONCLUSION
Evidence from this nationwide cohort study suggests that BB treatment beyond 1 year of MI for patients without heart failure or LVSD was not associated with improved cardiovascular outcomes.
Topics: Humans; Female; Middle Aged; Male; Cohort Studies; Myocardial Infarction; Heart Failure; Ventricular Dysfunction, Left; Hospitalization; Adrenergic beta-Antagonists
PubMed: 37130746
DOI: 10.1136/heartjnl-2022-322115 -
Ultrasound (Leeds, England) Nov 2019The aim of this study was to prospectively evaluate the diagnostic performance of strain elastography for the assessment of liver fibrosis in patients with chronic liver...
The aim of this study was to prospectively evaluate the diagnostic performance of strain elastography for the assessment of liver fibrosis in patients with chronic liver disease using Ishak (0-6) histology stage as a reference standard. Ninety-eight consecutive patients with suspected chronic liver disease scheduled for liver biopsy (n = 78) or histologically confirmed cirrhosis (n = 20) were enrolled. Liver fibrosis Index (LF Index) calculated by strain elastography, liver stiffness by transient elastography and serum fibrosis markers (aspartate aminotransferase-to-platelet ratio index and King's Score) were measured. Spearman's correlation coefficient between the LF Index, liver stiffness, serum fibrosis markers and fibrosis stage were calculated and compared using areas under the receiver-operating characteristics (AUROCs) curves. Among 73 patients who underwent strain elastography, there was weak correlation between fibrosis stage and the LF Index (Spearman's: ρ = 0.385 for Ishak score; = 0.001). Among 52 patients who underwent strain elastography and transient elastography, the AUROC values using LF Index, transient elastography, aspartate aminotransferase-to-platelet ratio index and King's Score for diagnosing significant fibrosis (Ishak score ≥ 3) were 0.79, 0.87, 0.86 and 0.85, respectively (0.0001) and for diagnosing severe fibrosis/cirrhosis (Ishak score ≥ 5) were 0.83, 0.94, 0.92 and 0.92, respectively ( < 0.0001). When comparing the diagnostic performance using LF Index, transient elastography, aspartate aminotransferase-to-platelet ratio index and King's Score, transient elastography shows a significantly higher AUROC value than LF Index in detecting severe fibrosis ( = 0.0149). The diagnostic performance of LF Index calculated by strain elastography was not statistically significantly different to the other noninvasive tests for the assessment of significant liver fibrosis but inferior to transient elastography for the assessment of severe fibrosis/cirrhosis.
PubMed: 31762783
DOI: 10.1177/1742271X19862836 -
Journal of Clinical and Translational... Apr 2023Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We...
BACKGROUND AND AIMS
Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV).
METHODS
Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment.
RESULTS
A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), =0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), =0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, =0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, =0.031).
CONCLUSIONS
ETV combined with ALHX increased liver fibrosis regression in CHB patients.
PubMed: 36643032
DOI: 10.14218/JCTH.2022.00091