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Liver Transplantation : Official... Dec 2022Patients with indeterminate liver nodules, classified as LR-3 and LR-4 observations per the Liver Imaging Reporting and Data System, are at risk of developing...
Clinical outcomes of patients with Liver Imaging Reporting and Data System 3 or Liver Imaging Reporting and Data System 4 observations in patients with cirrhosis: A systematic review.
Patients with indeterminate liver nodules, classified as LR-3 and LR-4 observations per the Liver Imaging Reporting and Data System, are at risk of developing hepatocellular carcinoma (HCC), but risk estimates remain imprecise. We conducted a systematic review of Ovid MEDLINE, EMBASE, and Cochrane databases from inception to December 2021 to identify cohort studies examining HCC incidence among patients with LR-3 or LR-4 observations on computed tomography (CT) or magnetic resonance imaging (MRI). Predictors of HCC were abstracted from each study, when available. Of 13 total studies, nine conducted LR-3 observation-level analyses, with the proportions of incident HCC ranging from 1.2% to 12.5% at 12 months and 4.2% to 44.4% during longer study follow-up. Among three studies with patient-level analyses, 8%-22.2% of patients with LR-3 lesions developed LR-4 observations and 11.1%-24.5% developed HCC. Among nine studies conducting LR-4 observation-level analyses, incident HCC ranged from 30.8% to 44.0% at 12 months and 30.9% to 71.0% during study follow-up; conversely, 6%-42% of observations were downgraded to LR-3 or lower. Patient-level factors associated with HCC included older age, male sex, higher alpha-fetoprotein levels, viral etiology, and prior history of HCC; observation-level factors included maximum diameter, threshold growth, T2 hyperintensity, and visibility on ultrasound. Studies were limited by small sample sizes, inclusion of patients with prior HCC, short follow-up duration, and failure to account for clustering of observations in patients or competing risks of transplantation and death. LR-3 and LR-4 observations have elevated but variable risks of HCC. Higher quality studies are necessary to identify high-risk patients who warrant close CT or MRI-based follow-up.
Topics: Humans; Male; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Liver Transplantation; Liver Cirrhosis; Magnetic Resonance Imaging; Contrast Media; Sensitivity and Specificity
PubMed: 35980600
DOI: 10.1002/lt.26562 -
International Journal of Surgery... Aug 2018Hepatocellular carcinoma (HCC) is one of most common causes for cancer-related death around the world. Epithelial cell adhesion molecule (EpCAM) is established as a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatocellular carcinoma (HCC) is one of most common causes for cancer-related death around the world. Epithelial cell adhesion molecule (EpCAM) is established as a vital prognostic factor for the human malignant tumors. However, the potential role of EpCAM in HCC has largely remained elusive. Herein we aimed to gain insight into the clinicopathological and prognostic role of EpCAM in HCC.
METHODS AND MATERIALS
The PubMed, Web of Science, EMBASE and SCOPUS databases were systematically searched from their inception up to 5 December 4, 2017. The hazard ratio (HR) and odds ratio (OR) were respectively used as the effect size to explore the associations between EpCAM expression and the prognosis and clinicopathological features in HCC patients.
RESULTS
Sixteen studies recruiting 2488 HCC patients were included in the meta-analysis, of which the publication year ranging from 2011 to 2017. As a result, the pooled HR of 1.634 indicated that higher EpCAM expression was significantly associated with the shorter overall survival (OS) periods (95%CIs: 1.151-2.320; Z = 2.740, P = 0.006). Next, a meta-analysis of disease-free survival (DFS) was performed for the ten studies. Consequently, for the p-value less than 0.05 for the combined HR, the overexpression of EpCAM was significantly correlated with poorer DFS. Next, the results derived from our study suggest that the overexpression of EpCAM is associated with the clinicopathological features of HCC, including poorer tumor differentiation and high alpha-fetoprotein (AFP) levels.
CONCLUSION
The results derived from our study suggest that the overexpression of EpCAM is associated with the clinicopathological features of HCC, including poorer differentiation and high AFP levels. More importantly, overexpression of EpCAM was confirmed as the unfavorable predictor for the shorter OS and DFS for HCC patients.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Disease-Free Survival; Epithelial Cell Adhesion Molecule; Female; Humans; Liver Neoplasms; Neoplasm Proteins; Odds Ratio; Prognosis; Proportional Hazards Models
PubMed: 29936198
DOI: 10.1016/j.ijsu.2018.06.025 -
Journal of Clinical Medicine Jan 2023Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its... (Review)
Review
Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the , , , , , and databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78-0.85), 0.89 (95%CI: 0.85-0.91), and 0.92 (95%CI: 0.89-0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66-0.79)) and a high specificity (0.87 (95%CI: 0.81-0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66-0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66-0.87), 0.80 (95%CI: 0.72-0.87), and 0.86 (95%CI: 0.83-0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality.
PubMed: 36769597
DOI: 10.3390/jcm12030949 -
Clinical and Experimental Medicine Feb 2022A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option.
METHODS
Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels.
RESULTS
Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.50-0.79), cabozantinib (HR = 0.76, 95% CI = 0.63-0.92), and ramucirumab (HR = 0.82, 95% CI = 0.70-0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR = 0.44, 95% CI = 0.36-0.52), regorafenib (HR = 0.46, 95% CI = 0.37-0.56), ramucirumab (HR = 0.54, 95% CI = 0.43-0.68), brivanib (HR = 0.56, 95% CI = 0.42-0.76), S-1 (HR = 0.60, 95% CI = 0.46-0.77), axitinib (HR = 0.62, 95% CI = 0.44-0.87), and pembrolizumab (HR = 0.72, 95% CI = 0.57-0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients' stratification.
CONCLUSIONS
The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC.
Topics: Bayes Theorem; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Network Meta-Analysis; Sorafenib
PubMed: 34146196
DOI: 10.1007/s10238-021-00727-7 -
World Journal of Gastroenterology Sep 2020Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging...
BACKGROUND
Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC.
AIM
To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival.
METHODS
A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre.
RESULTS
There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival ( = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival ( = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant ( = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.
CONCLUSION
NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.
Topics: Albumins; Bilirubin; Carcinoma, Hepatocellular; Child; Humans; Liver Neoplasms; Lymphocytes; Neutrophils; Prognosis; Retrospective Studies
PubMed: 32952347
DOI: 10.3748/wjg.v26.i33.5022 -
The Turkish Journal of Gastroenterology... Mar 2020Previous study has shown a positive relationship between the hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and cholangiocarcinoma (CCA); however, their... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Previous study has shown a positive relationship between the hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and cholangiocarcinoma (CCA); however, their correlation with different anatomical sites of CCA (i.e. ICC and ECC) has not been revealed. This study aims to evaluate the association of HBV or HCV infection with CCA, including the intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), and to determine the roles of α-1 fetoprotein (AFP), CA19-9, and lymph node involvement in CCA with HBV infection.
MATERIALS AND METHODS
Relevant studies published between 2004 and 2016 were systematically searched and retrieved from PubMed, SpringerLink, and Science Direct using key terms such as "cholangiocarcinoma", "bile duct cancer", "extrahepatic cholangiocarcinoma", and "intrahepatic cholangiocarcinoma". The demographic, clinical, and laboratory data were extracted from the included studies, and the meta-analysis was performed using RevMan and STATA 11.0 software.
RESULTS
A total of 13 studies with CCA matched the inclusion criteria in this meta-analysis, including 7,113 CCA patients and 24,763 controls. This meta-analysis showed that the HBV or HCV infections can significantly increase the risk of CCA, including ICC and ECC. In addition, the higher levels of AFP, lower levels of CA19-9, and lymph node involvement were detected in the CCA patients with HBV infection as compared to those without.
CONCLUSION
The HBV and HCV infections significantly increased the risk of CCA, as well as ICC and ECC. The involvement of AFP, CA19-9, and lymph nodes may play an important role in the diagnosis of CCA.
Topics: Adult; Aged; Antigens, Tumor-Associated, Carbohydrate; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Female; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Lymph Nodes; Male; Middle Aged; Risk Factors; alpha-Fetoproteins
PubMed: 32343237
DOI: 10.5152/tjg.2020.19056 -
Therapeutic Advances in Gastroenterology 2024Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to...
BACKGROUND
Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to explore the efficacy of these treatments in phase III randomized clinical trials.
OBJECTIVES
The goal is to identify which patients are most likely to benefit significantly from these emerging therapies, contributing to more personalized and informed clinical decision-making.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES AND METHODS
PubMed, Embase, ClinicalTrials.gov, and international conference databases have been searched from 1 January 2010 to 1 December 2023.
RESULTS
After screening, 17 phase III trials encompassing 18 treatments were included. In the whole-population network meta-analysis, the newly first-line tremelimumab plus durvalumab (Tre + Du) was found to be comparable with atezolizumab plus bevacizumab (Atezo + Beva) in providing the best overall survival (OS) benefit [hazard ratio (HR) 1.35, 95% confidence interval (CI): 0.93-1.92]. Concerning OS benefits, sintilimab plus bevacizumab biosimilar (Sint + Beva), camrelizumab plus rivoceranib (Camre + Rivo), and lenvatinib plus pembrolizumab (Lenva + Pemb) appear to exhibit similar effects to Tre + Du and Atezo + Beva. In the context of progression-free survival, Atezo + Beva seemed to outperform Tre + Du (HR: 0.66 CI: 0.49-0.87), while the effects are comparable to Sint + Beva, Camre + Rivo, and Lenva + Pemb. Upon comparison between Asia-Pacific and non-Asia-Pacific cohorts, as well as between hepatitis B virus (HBV)-infected and non-HBV-infected populations, immune checkpoint inhibitor (ICI)-based treatments seemed to exhibit heightened efficacy in the Asia-Pacific group and among individuals with HBV infection. However, combined ICI-based therapies did not show more effectiveness than molecular-targeted drugs in patients without macrovascular invasion and/or extrahepatic spread. As for grades 3-5 adverse events, combined therapies showed comparable safety to sorafenib and lenvatinib.
CONCLUSION
Compared with sorafenib and lenvatinib, combination therapies based on ICIs significantly improved the prognosis of advanced HCC and demonstrated similar safety. At the same time, the optimal treatment approach should be tailored to individual patient characteristics, such as etiology, tumor staging, and serum alpha-fetoprotein levels. With lower incidence rates of treatment-related adverse events and non-inferior efficacy compared to sorafenib, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI-combined therapies.
TRIAL REGISTRATION
PROSPERO, CRD42022288172.
PubMed: 38645513
DOI: 10.1177/17562848241237631 -
Cancer Medicine Apr 2024Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the association between the prognosis of HCC and their expression remained unclear. The purpose of this meta-analysis was to determine the prognostic significance of lncRNA SNHGs in HCC.
METHODS
We systematically searched Embase, Web of Science, PubMed, and Cochrane Library for eligible articles published up to February 2024. The prognostic significance of SNHGs in HCC was evaluated by hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) were used to assess the clinicopathological features of SNHGs.
RESULTS
This analysis comprised a total of 25 studies covering 2314 patients with HCC. The findings demonstrated that over-expressed SNHGs were associated with larger tumor size, multiple tumor numbers, poor histologic grade, earlier lymphatic metastasis, vein invasion, advanced tumor stage, portal vein tumor thrombosis (PVTT), and higher alpha-fetoprotein (AFP) level, but not with hepatitis B virus (HBV) infection, and cirrhosis. In terms of prognosis, patients with higher SNHG expression were more likely to have shorter overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS).
CONCLUSIONS
In conclusion, upregulation of SNHGs expression correlates with shorter OS, RFS, DFS, tumor size and numbers, histologic grade, lymphatic metastasis, vein invasion, tumor stage, PVTT, and AFP level, suggesting that SNHGs may serve as prognostic biomarkers in HCC.
Topics: Humans; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Recurrence, Local; Prognosis; RNA, Long Noncoding; RNA, Small Nucleolar
PubMed: 38634194
DOI: 10.1002/cam4.7200 -
Medicine Aug 2019Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not consistent. This meta-analysis aimed to explore the relationship between AFP response and clinical outcomes of HCC.
METHODS
PubMed, Embase, Medline and Cochrane library were searched for relevant articles published before March 20, 2019. The data were analyzed using RevMan5.3 software.
RESULTS
Twenty-nine articles with 4726 HCC patients were finally included for analysis. The pooled results showed that post-treatment AFP response was significantly associated with overall survival (OS) (hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.35-0.47, P <.001), progression free survival (PFS) (HR = 0.46, 95% CI: 0.39-0.54, P <.001) and recurrence free survival (RFS) (HR = 0.41, 95% CI: 0.29-0.56, P <.001) of HCC patients.
CONCLUSION
post-treatment AFP response might be a useful prognostic marker for HCC patients.
Topics: Humans; Liver Neoplasms; Prognosis; alpha-Fetoproteins
PubMed: 31374020
DOI: 10.1097/MD.0000000000016557 -
Bioscience Reports Mar 2020Midkine (MDK) has been proposed as one of the most promising markers for hepatocellular carcinoma (HCC). This meta-analysis was conducted to compare the diagnostic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Midkine (MDK) has been proposed as one of the most promising markers for hepatocellular carcinoma (HCC). This meta-analysis was conducted to compare the diagnostic accuracy of MDK and α-fetoprotein (AFP) for HCC.
METHODS
We systematically searched PubMed/MEDLINE, Ovid/EMBASE, and the Cochrane Library for all relevant studies up to 18 May 2019. The Revised Quality Assessment for Studies of Diagnostic Accuracy tool (QUADAS-2) was used to assess the methodological quality of the included studies. The sensitivity, specificity, and the area under the curve (AUC) of MDK and AFP for detecting HCC were pooled using random-effects model.
RESULTS
Seventeen studies from five articles with a total of 1122 HCC patients and 2483 controls were included. The summary estimates using MDK and AFP for detecting HCC were as follows: sensitivity, 85 vs 52%, specificity, 82 vs 94%, and AUC, 0.90 vs 0.83. The summary estimates using MDK and AFP for detecting hepatitis virus-related HCC as follows: sensitivity, 93 vs 74%, specificity, 85 vs 97%, and AUC, 0.95 vs 0.97. The summary estimates using MDK and AFP for detecting early-stage HCC were as follows: sensitivity, 83.5 vs 44.4%, specificity, 81.7 vs 84.8%, and AUC, 0.87 vs 0.52. The summary estimates using MDK for detecting AFP-negative HCC as follows: sensitivity, 88.5%, specificity, 83.9%, and AUC, 0.91.
CONCLUSION
MDK is more accurate than AFP in diagnosing HCC, especially for early-stage HCC and AFP-negative HCC. Both MDK and AFP had excellent diagnostic performance for hepatitis virus-related HCC.
Topics: Area Under Curve; Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Midkine; ROC Curve; alpha-Fetoproteins
PubMed: 32039435
DOI: 10.1042/BSR20192424