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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 -
Acta Obstetricia Et Gynecologica... Apr 2024Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis... (Review)
Review
INTRODUCTION
Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis or chronic hepatitis B virus infection. Ultrasound evaluation, CT scan, and MRI are used to detect HCC. α-fetoprotein (AFP) is a common marker used to detect HCC in the non-pregnant population, which notoriously increases in pregnant women in relation to gestational age. Treatment is driven by the extent of the disease and the severity of underlying liver disease. Pregnancy may represent an obstacle to diagnosis and appropriate treatment of HCC. The aim of this descriptive systematic review was to describe the clinical features and maternal and neonatal outcomes of HCC in pregnancy.
MATERIAL AND METHODS
We performed a systematic review of the literature about HCC diagnosed in pregnancy and the postpartum period, with signs or symptoms arising in pregnancy. We included case reports and case series describing the clinical features of women diagnosed with HCC, fibrolamellar variant of HCC, and mixed HCC and cholangiocarcinoma during pregnancy or the postpartum period (with onset of symptoms during pregnancy), from inception to March 2023. The study protocol was registered with the PROSPERO database (Registration number: ID CRD42021275584).
RESULTS
We identified 180 records. The articles included in this systematic review were 47 case reports and 5 case series, for a total of 63 pregnancies. The two most frequent predisposing conditions were hepatitis B virus infection (30/63; 47%) and liver cirrhosis (14/63; 22%). Ultrasound evaluation was the most used technique to detect HCC. AFP was higher than normal in 28/46 patients tested (61%). Surgical treatment was the most used therapy, both during pregnancy and after delivery. Twenty-six patients (26/63; 42%) died within 6 months of diagnosis. Survival >24 months was 9% (4/46) in symptomatic and 29% (5/17) in asymptomatic women. No patient with cirrhotic liver survived more than 12 months. Thirty-eight newborns were alive at 28 days of age (38/63; 61%).
CONCLUSIONS
Hepatocellular carcinoma in pregnancy is associated with a high risk of maternal and neonatal mortality. Diagnosis in asymptomatic high-risk women or following abnormal maternal serum AFP screening is associated with better maternal outcomes.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Hepatitis B, Chronic; Liver Cirrhosis
PubMed: 37533304
DOI: 10.1111/aogs.14640 -
Frontiers in Immunology 2023To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis.... (Meta-Analysis)
Meta-Analysis
Development and validation of prognostic risk prediction models for hepatocellular carcinoma patients treated with immune checkpoint inhibitors based on a systematic review and meta-analysis of 47 cohorts.
OBJECTIVE
To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis. And to construct prediction models to aid in the prediction and improvement of prognosis.
METHODS
We searched PubMed, Embase, Web of Science and Cochrane Library for relevant studies from inception to March 29, 2023. After completing literature screening and data extraction, we performed meta-analysis, sensitivity analysis, and subgroup analysis to identify risk factors associated with OS and PFS. Using the pooled hazard ratio value for each risk factor, we constructed prediction models, which were then validated using datasets from 19 centers in Japan and two centers in China, comprising a total of 204 patients.
RESULTS
A total of 47 studies, involving a total of 7649 ICI-treated HCC patients, were included in the meta-analysis. After analyzing 18 risk factors, we identified AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number, vascular invasion and combination therapy as predictors for OS prediction model, while AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number and vascular invasion were selected as predictors for PFS model. To validate the models, we scored two independent cohorts of patients using both prediction models. Our models demonstrated good performance in these cohorts. In addition, in the pooled cohort of 204 patients, Our models also showed good performance with area under the curve (AUC) values of 0.712, 0.753, and 0.822 for the OS prediction model at 1-year, 2-year, and 3-year follow-up points, respectively, and AUC values of 0.575, 0.749 and 0.691 for the PFS prediction model Additionally, the calibration curve, decision curve analysis, and Kaplan-Meier curves in the pooled cohort all supported the validity of both models.
CONCLUSION
Based on the meta-analysis, we successfully constructed the OS and PFS prediction models for ICI-treated HCC patients. We also validated the models externally and observed good discrimination and calibration. The model's selected indicators are easily obtainable, making them suitable for further application in clinical practice.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Immune Checkpoint Inhibitors; Liver Neoplasms; alpha-Fetoproteins
PubMed: 37520554
DOI: 10.3389/fimmu.2023.1215745 -
World Journal of Surgical Oncology Feb 2024Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 90% of cases worldwide and a significant contributor to cancer-related deaths.... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of laparoscopic liver resection versus radiofrequency ablation in patients with early and small hepatocellular carcinoma: an updated meta-analysis and meta-regression of observational studies.
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 90% of cases worldwide and a significant contributor to cancer-related deaths. This study comprehensively compares the safety and efficacy of laparoscopic liver resection (LLR) versus laparoscopic or percutaneous radiofrequency ablation (LRFA or PRFA) in patients with early and small HCC.
METHODS
We systematically searched Cochrane Library, PubMed, Scopus, and Web of Science databases to include studies comparing LLR versus LRFA or PRFA in patients with early HCC meets the Milan criteria (defined as solitary nodule < 5 cm or three nodules ≤ 3 cm with no extrahepatic spread or vascular invasion). Pooled results were examined for overall survival, disease-free survival, recurrence-free survival, local, intrahepatic and extrahepatic recurrence rates, and complications. We conducted subgroup analyses based on the type of RFA. Meta-regression analyzed the association between overall survival, local recurrence, and various factors. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. We analyzed the data using the R (v.4.3.0) programming language and the "meta" package of RStudio software.
RESULTS
We included 19 observational studies, compromising 3756 patients. LLR showed higher 5-year overall survival compared to RFA (RR = 1.17, 95% CI [1.06, 1.3], P > 0.01). Our subgroup analysis showed that LLR had higher 5-year survival than PRFA (RR = 1.15, 95% CI [1.02, 1.31], P = 0.03); however, there was no significant difference between LLR and LRFA (RR = 1.26, 95% CI [0.98, 1.63], P = 0.07). LLR was associated with higher disease-free survival) RR = 1.19, 95% CI [1.05, 1.35], P < 0.01; RR = 1.61, 95% CI [1.31, 1.98], P < 0.01(and recurrence-free survival) RR = 1.21, 95% CI [1.09, 1.35], P < 0.01; RR = 1.45, 95% CI [1.15, 1.84], P < 0.01(at 1 and 3 years. LLR was associated with lower local (RR = 0.28, 95% CI [0.16, 0.47], P < 0.01) and intrahepatic recurrence (RR = 0.7, 95% CI [0.5, 0.97], P = 0.03) than RFA. However, complications were significantly higher with LLR (RR = 2.01, 95% CI [1.51, 2.68], P < 0.01). Our meta-regression analysis showed that younger patients had higher risk for local recurrence (P = 0.008), while age wasn't significantly linked to overall survival (P = 0.25). Other covariates like total bilirubin, alpha-fetoprotein levels, and tumor size also showed no significant associations with either overall survival or local recurrence.
CONCLUSION
LLR offers improved long-term outcomes and lower recurrence rates than PRFA. However, no significant distinctions were observed between LRFA and LLR in overall survival, recurrence-free survival, and local recurrence. More robust well-designed RCTs are essential to validate our findings.
Topics: Humans; Carcinoma, Hepatocellular; Hepatectomy; Laparoscopy; Liver Neoplasms; Neoplasm Recurrence, Local; Radiofrequency Ablation; Retrospective Studies; Treatment Outcome
PubMed: 38326841
DOI: 10.1186/s12957-023-03292-3 -
Updates in Surgery Dec 2023Anal fistula (AF) is a common disease with high prevalence and surgical operations are effective treatments in clinical work. There exist many well-known surgical... (Meta-Analysis)
Meta-Analysis Review
Anal fistula (AF) is a common disease with high prevalence and surgical operations are effective treatments in clinical work. There exist many well-known surgical techniques treating complex anal fistula (CAF), however, none is ideal. To compare the superiority of Anal fistula plug (AFP) and Endoanal advancement flap repair (EAFR) for complex anal fistula. We searched worldwide databases including Pubmed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and SinoMed from their inception to March 2023. Studies comparing the outcomes of AFP and EAFR were included according to the PICO principles. The indicators of the healing rate, recurrence rate, wound infection rate, and complication rate, et al. were extracted and compared between different surgical methods. 5 RCTS and 7 non-RCTs were included in the meta-analysis with a total of 847 patients (341 patients conducted with AFP and 506 patients with EAFR). By combining the total effect of the 12 articles, we found that there was a statistical difference reporting the healing rate of AFP 48.3% and EAFR 64.4% treating the CAF (OR 0.68, 95% CI 0.30,1.55, P = 0.03), and EAFR has a better healing rate. However, there was no significant difference in terms of the recurrence rate (OR 1.68, 95% CI 0.80,3.54, P = 0.17), the wound infection rate (OR 1.82, 95% CI 0.95,3.52, P = 0.07), and the complication rate (OR 1.06, 95% CI 0.70,1.61, P = 0.77) either in the 12 articles or in the subgroup. The meta-analysis indicated that the EAFR was superior to AFP in terms of the healing rate treating the CAF, however, there were no significant differences between the two groups when it came to the recurrence rate, the wound infection rate, and the complication rate. EAFR might be one initial treatment for the complex cryptoglandular anal fistulas compared with AFP.
Topics: Humans; alpha-Fetoproteins; Rectal Fistula; Treatment Outcome; Surgical Flaps; Fecal Incontinence; Wound Infection; Anal Canal
PubMed: 37882975
DOI: 10.1007/s13304-023-01674-6 -
Frontiers in Artificial Intelligence 2023Hepatocellular carcinoma is a malignant neoplasm of the liver and a leading cause of cancer-related deaths worldwide. The multimodal data combines several modalities,...
BACKGROUND
Hepatocellular carcinoma is a malignant neoplasm of the liver and a leading cause of cancer-related deaths worldwide. The multimodal data combines several modalities, such as medical images, clinical parameters, and electronic health record (EHR) reports, from diverse sources to accomplish the diagnosis of liver cancer. The introduction of deep learning models with multimodal data can enhance the diagnosis and improve physicians' decision-making for cancer patients.
OBJECTIVE
This scoping review explores the use of multimodal deep learning techniques (i.e., combining medical images and EHR data) in diagnosing and prognosis of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA).
METHODOLOGY
A comprehensive literature search was conducted in six databases along with forward and backward references list checking of the included studies. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for scoping review guidelines were followed for the study selection process. The data was extracted and synthesized from the included studies through thematic analysis.
RESULTS
Ten studies were included in this review. These studies utilized multimodal deep learning to predict and diagnose hepatocellular carcinoma (HCC), but no studies examined cholangiocarcinoma (CCA). Four imaging modalities (CT, MRI, WSI, and DSA) and 51 unique EHR records (clinical parameters and biomarkers) were used in these studies. The most frequently used medical imaging modalities were CT scans followed by MRI, whereas the most common EHR parameters used were age, gender, alpha-fetoprotein AFP, albumin, coagulation factors, and bilirubin. Ten unique deep-learning techniques were applied to both EHR modalities and imaging modalities for two main purposes, prediction and diagnosis.
CONCLUSION
The use of multimodal data and deep learning techniques can help in the diagnosis and prediction of HCC. However, there is a limited number of works and available datasets for liver cancer, thus limiting the overall advancements of AI for liver cancer applications. Hence, more research should be undertaken to explore further the potential of multimodal deep learning in liver cancer applications.
PubMed: 37965284
DOI: 10.3389/frai.2023.1247195 -
Frontiers in Immunology 2024It is unclear whether the systemic inflammation response index (SIRI) can predict the prognosis of patients with hepatocellular carcinoma (HCC). Consequently, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is unclear whether the systemic inflammation response index (SIRI) can predict the prognosis of patients with hepatocellular carcinoma (HCC). Consequently, the present study focused on systematically identifying the relationship between SIRI and the prognosis of patients with HCC through a meta-analysis.
METHODS
Systematic and comprehensive studies were retrieved from PubMed, Web of Science, Embase, and the Cochrane Library from their inception to August 10, 2023. The role of SIRI in predicting overall survival (OS) and progression-free survival (PFS) in HCC was determined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) and 95% CIs were pooled to analyze the correlations between SIRI and the clinicopathological features of HCC.
RESULTS
Ten articles involving 2,439 patients were included. An elevated SIRI was significantly associated with dismal OS (HR=1.75, 95% CI=1.52-2.01, p<0.001) and inferior PFS (HR=1.66, 95% CI=1.34-2.05, p<0.001) in patients with HCC. Additionally, according to the combined results, the increased SIRI was significantly related to multiple tumor numbers (OR=1.42, 95% CI=1.09-1.85, p=0.009) and maximum tumor diameter >5 cm (OR=3.06, 95% CI=1.76-5.30, p<0.001). However, the SIRI did not show any significant relationship with sex, alpha-fetoprotein content, Child-Pugh class, or hepatitis B virus infection.
CONCLUSION
According to our results, elevated SIRI significantly predicted OS and PFS in patients with HCC. Moreover, the SIRI was significantly associated with tumor aggressiveness.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/inplasy-2023-9-0003/, identifier INPLASY202390003.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Liver Neoplasms; Progression-Free Survival; Inflammation
PubMed: 38469315
DOI: 10.3389/fimmu.2024.1291840 -
Frontiers in Oncology 2024Portal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global...
BACKGROUND
Portal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global consensus or standard guidelines on the management of hepatocellular carcinoma (HCC) with PVTT. Increasing evidence suggests that more aggressive treatment modalities, including transarterial chemoembolization, radiotherapy, targeted therapy, and various combination therapies, may improve the prognosis and prolong the survival of advanced hepatocellular carcinoma (aHCC) patients with PVTT. We aim to comprehensively review and compare the efficacy and safety of these advanced options for aHCC with PVTT.
METHODS
A comprehensive literature search was conducted on PubMed and EMBASE for phase II or III randomized controlled trials (RCTs) investigating multimodality treatments for aHCC with PVTT. Kaplan-Meier curves for overall survival (OS) and progression-free survival were constructed to retrieve individual patient-level data to strengthen the comparison of the benefits of all multimodality treatments of interest. Each study was pooled in a fixed-effects network meta-analysis (NMA). We also conducted subgroup analyses using risk ratios extracted from each study, including viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion or portal vein tumor thrombosis, and extrahepatic spread. Multimodality treatments were ranked using SUCRA scores.
RESULTS
We identified 15 randomized controlled trials with 16 multimodality regimens that met the inclusion criteria. Among them, 5,236 patients with OS results and 5,160 patients with PFS results were included in the analysis. The hepatic arterial infusion chemotherapy of fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) showed OS and PFS benefits over all the other therapies. In terms of OS, HAIC-FO, nivolumab, and TACE+Len were superior to sorafenib, lenvatinib, and donatinib monotherapies, as well as HAIC-FO+Sor. In terms of PFS, TACE+Len showed better benefits than lenvatinib, donatinib, and tremelimumab+durvalumab. A low heterogeneity ( < 50%) and consistency were observed. The SUCRA score for OS ranked HAIC-FO+sorafenib as the best treatment option among all multimodality treatments in hepatitis B, MVI, or PVTT with EHS and AFP 400 μg/L subgroups.
CONCLUSION
HAIC-FO and HAIC-FO+sorafenib are statistically better options for unresectable hepatocellular carcinoma with PVTT among the multimodality treatments, and their effective and safe implementation may provide the best outcomes for HCC-PVTT patients.
PubMed: 38434681
DOI: 10.3389/fonc.2024.1344798 -
International Journal of Molecular... Jan 2024Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like... (Meta-Analysis)
Meta-Analysis Review
Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients. However, the lack of a standardized workflow protocol has hampered holistic comparisons across the literature. Consequently, we herein confined our meta-analysis to only a subset of these lncRNAs. The combined analysis of serum (HULC) gene expression with (HOTAIR) and (UCA1) demonstrated markedly enhanced sensitivity and specificity in diagnostic capability compared to traditional biomarkers or other ncRNAs. These findings could have substantial implications for the early diagnosis and tailored treatment of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; RNA, Long Noncoding; Genes, Homeobox; RNA, Antisense; Carcinoma, Transitional Cell; Gene Expression Regulation, Neoplastic; Urinary Bladder Neoplasms; RNA, Untranslated; Biomarkers; Gene Expression Profiling; Biomarkers, Tumor
PubMed: 38279264
DOI: 10.3390/ijms25021258 -
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