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Transplantation Reviews (Orlando, Fla.) Jan 2022Data on predictors of post-recurrence survival (PRS) of recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) have not been reviewed and analysed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Data on predictors of post-recurrence survival (PRS) of recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) have not been reviewed and analysed systematically. We aimed to systematically analyse all published data on the predictors for PRS.
METHODS
In accordance with PRISMA and MOOSE guidelines, online search of PubMed and EMBASE databases was done for all reports that evaluate the predictors of PRS based on multivariate analyses. Cumulative analyses of hazard ratios (HRs) and their corresponding 95% CIs were conducted to assess the potential predictors of PRS.
RESULTS
Twenty-three studies met the inclusion criteria. Among the 11,868 patients involved, 1921 (16%) had HCC recurrence within a median time of 16 months. The following were recurrence and tumour-related predictors: time to recurrence (<1 year; HR: 1.97; p < 0.001), AFP level at recurrence(≥100 ng/ml; HR: 1.82; p < 0.001), multiple recurrence (HR: 1.22; p < 0.001), bone recurrence (HR: 2.10; p < 0.001), poor differentiation (HR: 1.52; p < 0.001), intrahepatic recurrence (HR: 0.91; p = 0.03), extrahepatic recurrence (HR: 1.87; p < 0.001), Milan criteria at LT (HR: 1.34; p < 0.001), microvascular invasion (HR: 1.59; p < 0.001), multiorgan recurrence (HR: 1.28; p < 0.001), and recurrent HCV infection (HR: 1.21; p < 0.001). The treatment-related predictors were as follows: surgical resection (HR: 0.33; p < 0.001), mTOR inhibitors (HR: 0.63; p < 0.001), sorafenib (HR: 1.00; p = 0.01), palliative treatment (HR: 3.07; p < 0.001), RFA (HR: 0.47; p < 0.001), and radiotherapy (HR: 1.19; p < 0.001).
CONCLUSIONS
Systematic evaluation of these predictors could guide surgeons to design risk-adapted algorithms for the management of post-LT HCC recurrence to construct reliable predictive models and to design future prospective studies or clinical trials.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local; Prospective Studies; Retrospective Studies; Risk Factors; alpha-Fetoproteins
PubMed: 34999555
DOI: 10.1016/j.trre.2021.100676 -
European Journal of Obstetrics,... Jul 2020In women with twin pregnancies biomarkers are not used to predict preterm birth in clinical practice. This systematic review assessed the risk of both spontaneous and... (Meta-Analysis)
Meta-Analysis Review
In women with twin pregnancies biomarkers are not used to predict preterm birth in clinical practice. This systematic review assessed the risk of both spontaneous and iatrogenic preterm birth in twin pregnancies based on biochemical predictors. We searched the electronic databases from January 1990 to June 2019 without language restrictions. All studies on twin pregnancies where biochemical predictors and preterm birth were evaluated were included. We reported our findings as odds ratio (OR) with 95 % confidence intervals (CI) and pooled the estimates using random-effects meta-analysis for various predictor thresholds. From 12,623 citations, we included 33 studies involving 6077 pregnancies. The odds of preterm birth <28 weeks (OR 12.06, 95 % CI 4.90-29.70, I = 0%), <32 weeks (OR 10.03, 95 % CI 6.11-16.47, I = 0%), <34 weeks (OR 6.26, 95 % CI 3.85-10.17, I = 30 %), <37 weeks (OR 5.34, 95 % CI 3.68-7.76, I = 15 %) and delivery within 14 days of testing (OR 13.95, 95 % CI 4.33-44.98, I = 0%) was increased among women with a positive fetal Fibronectin (fFN) test who were either symptomatic or asymptomatic for preterm birth. Similarly, higher odds of preterm birth was also seen among twin pregnancies asymptomatic for preterm birth with a positive fFN test at gestations <32 weeks (OR 10.54, 95 % CI 5.66-19.64, I = 19 %), < 34 weeks (OR 8.07, 95 % CI 5.28-12.33, I = 0%) and < 37 weeks (OR 6.21, 95 % CI 4.34-8.87, I = 0%). As for other biomarkers, a significantly higher odds of preterm birth <37 weeks was seen among women with elevated maternal serum human Chorionic Gonadotrophin (mshCG) (OR 1.51, 95 % CI 1.07-2.13, I = 0%), 25 Hydroxy Vitamin D level <75 nmol/l (OR 2.59, 95 % CI 1.35-4.95, I=NA), positive phosphorylated Insulin-like Growth Factor Binding Protein-1 (phIGFBP-1) (OR 4.23, 95 % CI 1.97-9.09, I = 0%) and in those with elevated Interleukin 8 (IL-8) (OR 3.13, 95 % CI 1.18-8.34, I=NA). A higher odds of preterm birth at <34 weeks gestation was seen among women with maternal serum Alpha fetoprotein (AFP)>3.5 MoM (OR 2.35, 95 % CI 1.12-4.96, I=NA) while higher odds of preterm birth at <32 weeks was seen among women with 25 Hydroxy Vitamin D level <75 nmol/l (OR 3.01, 95 % CI 1.26-7.19, I=NA). Delivery within seven days of testing was significantly increased in women with a positive Matrix Metallo Protein-8 (MMP-8) test (OR 10.59, 95 % CI 3.70-30.29, I=NA). Fetal Fibronectin is strongly associated with predicting preterm birth among women with twin pregnancies who are either asymptomatic or symptomatic for preterm birth as well as in those asymptomatic for preterm birth. Other biomarkers have shown a positive association in the prediction of preterm birth among women with twin pregnancies. Further studies are recommended to evaluate their role.
Topics: Female; Fibronectins; Gestational Age; Humans; Infant, Newborn; Odds Ratio; Pregnancy; Pregnancy, Twin; Premature Birth
PubMed: 32446146
DOI: 10.1016/j.ejogrb.2020.04.015 -
Arab Journal of Gastroenterology : the... Mar 2021The relationship between the alpha-fetoprotein (AFP) level and the prognosis of hepatocellular carcinoma (HCC) after surgical resection remains unknown. This study aims... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND STUDY AIMS
The relationship between the alpha-fetoprotein (AFP) level and the prognosis of hepatocellular carcinoma (HCC) after surgical resection remains unknown. This study aims to assess this relationship.
PATIENTS AND METHODS
PubMed and Web of Science were systematically utilised. Meta-analysis was conducted for the outcomes of the recurrence-free survival (RFS) and the overall survival (OS) by comparing the high AFP group with the low AFP group.
RESULTS
The studies included 61 manuscripts with 35,461 patients. The summary hazard ratio (HR) for RFS was 1.501 (95% CI 1.355-1.662; Z = 7.81, P < 0.00001) when comparing the high AFP group with the low AFP group. Sensitivity analysis only included adjusted HRs, with the summary HR being 1.563 (95% CI 1.381-1.768; Z = 7.10, P < 0.00001). The summary HR for OS was 1.565 (95% CI 1.439-1.701; Z = 10.52, P < 0.00001) when comparing two AFP groups. Sensitivity analysis showed that the summary HR was 1.611 (95% CI 1.456-1.782; Z = 9.24, P < 0.00001).
CONCLUSION
Our meta-analysis indicated that elevated serum AFP levels are associated with poor prognosis of HCC after surgical resection.
Topics: Carcinoma, Hepatocellular; Hepatectomy; Humans; Liver Neoplasms; Prognosis; alpha-Fetoproteins
PubMed: 33551350
DOI: 10.1016/j.ajg.2020.09.004 -
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 -
Journal of Ethnopharmacology Jan 2024Transcatheter arterial chemoembolization (TACE) is recommended as the first-line therapy for unresected primary liver cancer (PLC), but only partial patients could... (Meta-Analysis)
Meta-Analysis
ETHNOPHARMACOLOGICAL RELEVANCE
Transcatheter arterial chemoembolization (TACE) is recommended as the first-line therapy for unresected primary liver cancer (PLC), but only partial patients could benefit from TACE due to the serious adverse reactions. Clearing heat and resolving toxin (CHRT), one of most critical traditional Chinese medicine (TCM) therapeutic principles, has been widely used in the treatment of PLC patients especially after TACE. However, there is no enough clinical evidence to confirm the efficacy and safety of the combined therapy.
AIM OF THE STUDY
To comprehensively evaluate the efficacy and safety of the combined CHRT-CHF with TACE in the treatment of PLC.
MATERIALS AND METHODS
7 databases were searched from their inception until February 1, 2023. The primary outcomes included survival rate (1-, 2-year), objective response rate (ORR) and disease control rate (DCR), liver function indicators (AST, ALT), adverse reactions including fever, upper digestive tract side and myelosuppression, AFP were selected as the secondary outcomes. RevMan5.4 software was used to evaluate the quality of included studies; meta-analysis, subgroup analysis, meta-regression analysis, publication bias and trial sequential analyses (TSA) was conducted by Stata software 12.0.
RESULTS
There were 40 RCTs involving 3649 patients. Patients treated with TACE plus CHRT-CHF showed significantly better 1-, 2-year survival (respectively: OR, 2.23 [1.67-2.97]; OR, 2.13 [1.56-2.92]), ORR (OR, 2.14 [1.82-2.52]), DCR (OR, 2.13 [1.73-2.62]) compared with TACE alone. There was a decreased incidence of aspartate transaminase (AST), alanine transaminase (ALT), alpha-fetoprotein (AFP) and postembolization syndrome (PES) in patients receiving the combined TACE with CHRT-CHF compared with TACE alone. Subgroup analysis found that lower proportion (20-30%) of CHRT-CHF significantly enhanced survival rate and DCR, higher proportion (≥40%) of CHRT-CHF reduced PES after TACE treatment.
CONCLUSION
The efficacy and safety of the combined CHRT-CHF with TACE were validated in this meta-analysis, the optimal proportion of CHRT-CHF in enhancing the efficacy may be 20-30%; Additionally, higher proportion (≥40%) of CHRT-CHF appears to reduce PES after TACE treatment. The potential role of combined relative proportion of CHRT-CHF with TACE should be emphasized in clinic.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Chemoembolization, Therapeutic; Hot Temperature; Treatment Outcome
PubMed: 37625603
DOI: 10.1016/j.jep.2023.117072 -
Journal of Molecular Medicine (Berlin,... Jul 2024Liver cirrhosis due to nonalcoholic steatohepatitis (NASH) is a life-threatening condition with increasing incidence world-wide. Although its symptoms are unspecific, it... (Review)
Review
Liver cirrhosis due to nonalcoholic steatohepatitis (NASH) is a life-threatening condition with increasing incidence world-wide. Although its symptoms are unspecific, it can lead to decompensation events such as ascites, hepatic encephalopathy, variceal hemorrhage, and hepatocellular carcinoma (HCC). In addition, an increased risk for cardiovascular events has been demonstrated in patients with NASH. Pharmacological treatments for NASH cirrhosis are not yet available, one of the reasons being the lack in surrogate endpoints available in clinical trials of NASH cirrhosis. The feasibility of non-invasive prognostic biomarkers makes them interesting candidates as possible surrogate endpoints if their change following treatment would result in better outcomes for patients in future clinical trials of NASH cirrhosis. In this systematic literature review, a summary of the available literature on the prognostic performance of non-invasive biomarkers in terms of cardiovascular events, liver-related events, and mortality is outlined. Due to the scarcity of data specific for NASH cirrhosis, this review includes studies on NAFLD whose evaluation focuses on cirrhosis. Our search strategy identified the following non-invasive biomarkers with prognostic value in studies of NASH patients: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), enhanced liver fibrosis (ELF™), BARD (BMI, AST/ALT (alanine aminotransferase) ratio, diabetes), Hepamet Fibrosis Score (HFS), liver enzymes (AST + ALT), alpha-fetoprotein, platelet count, neutrophil to lymphocyte ratio (NLR), Lysyl oxidase-like (LOXL) 2, miR-122, liver stiffness, MEFIB (liver stiffness measured with magnetic resonance elastography (MRE) + FIB-4), and PNPLA3 GG genotype. The aim of the present systematic literature review is to provide the reader with a summary of the non-invasive biomarkers with prognostic value in NASH cirrhosis and give an evaluation of their utility as treatment monitoring biomarkers in future clinical trials.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Biomarkers; Prognosis
PubMed: 38753041
DOI: 10.1007/s00109-024-02448-2 -
Scandinavian Journal of Gastroenterology Apr 2022Hepatocellular carcinoma (HCC) lacks a suitable biomarker for minimally-invasive disease detection. Methylated (mSEPT9) is an emerging liquid biopsy test. We aimed to... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis: the diagnostic accuracy of methylated for the detection of hepatocellular carcinoma and the clinical evaluation of its use in combination with other surveillance modalities.
BACKGROUND
Hepatocellular carcinoma (HCC) lacks a suitable biomarker for minimally-invasive disease detection. Methylated (mSEPT9) is an emerging liquid biopsy test. We aimed to investigate recent studies that applied mSEPT9 for HCC diagnosis. Furthermore, we evaluated the combinations of other surveillance modalities for the detection of HCC.
METHODS
A systematic review was performed on the diagnostic accuracy of mSEPT9 for the detection of HCC. Using a bivariate model, the pooled sensitivity and specificity were calculated. Additionally, Fagan's nomograms were used to calculate the pre-test and post-test probabilities of HCC for various combinations of surveillance modalities.
RESULTS
Six full texts were included in the meta-analysis. The pooled sensitivity and specificity of mSEPT9 for the detection of HCC, were 0.80 (95% CI, 0.67-0.89) and 0.90 (95% CI, 0.84-0.94). The area under the receiver operating curve was 0.92. The probability of having HCC for the combinations of mSEPT9+ ultrasound scan (USS) and mSEPT9+ Alpha fetoprotein (AFP) were 0.7% and 1.2% respectively if both tests were negative (in a population with 10% HCC prevalence). The combination of USS and AFP would miss relatively fewer cancers for 1000 patients in comparison to other combinations of two surveillance modalities.
CONCLUSION
Test combinations have superior performance for the detection of HCC than any individual test. mSEPT9 has shown promise in the detection of HCC with higher estimates of performance accuracy. mSEPT9 has potential for use as an HCC surveillance modality in adjunct with other tests to improve detection rates. However, cost effectiveness of this approach needs further evaluation.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Sensitivity and Specificity; Ultrasonography; alpha-Fetoproteins
PubMed: 34957898
DOI: 10.1080/00365521.2021.2020331 -
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 -
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