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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 -
World Journal of Gastrointestinal... Apr 2024Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection...
BACKGROUND
Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.
AIM
To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.
METHODS
This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023.
RESULTS
Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC.
CONCLUSION
Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.
PubMed: 38660636
DOI: 10.4251/wjgo.v16.i4.1596 -
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 -
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 -
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 -
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 -
Cancer May 2024In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high...
BACKGROUND
In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high risk of death from liver failure. There is an unmet need for reliable alternative end points for clinical trials and daily clinical practice. To evaluate treatment response in patients with unresectable or metastatic hepatocellular carcinoma (mHCC), imaging-related end points are often used, whereas serologic end points have been developed for patients with serum alpha-fetoprotein levels >20 ng/mL. The objective of this study was to evaluate clinical trials that report concomitant assessment of radiographic and serologic response in patients with mHCC.
METHODS
After a systematic review, studies that evaluated response according to radiographic and serologic criteria were selected. A correlation between progression-free survival (PFS) and overall survival (OS) was performed, and a linear regression of each response-related outcome measure with OS was reported. Finally, the effect of eight baseline variables on OS and response-related measures was evaluated.
RESULTS
Twenty-six studies were included, including 16 first-line studies and 10 second-line studies. PFS and response rates demonstrated a significant relationship with OS, whereas disease control rates did not. The responses were correlated with OS, particularly in the first-line setting, after targeted therapy, and whenever assessment was early. Among the baseline variables, only performance status had a prognostic role, whereas hepatitis B virus-related liver disease was associated with higher radiographic response rates.
CONCLUSIONS
PFS and radiographic and serologic response rates appear to be reliable intermediate end points in patients with mHCC who are undergoing systemic antineoplastic therapy. However, the serologic response is available earlier.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Clinical Trials as Topic; Progression-Free Survival; Antineoplastic Agents; Treatment Outcome
PubMed: 38231887
DOI: 10.1002/cncr.35199 -
BMC Cancer Dec 2023The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes.
METHODS
We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type.
RESULTS
A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis.
CONCLUSIONS
CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.
Topics: Humans; Prognosis; Neoplastic Cells, Circulating; Disease-Free Survival; Progression-Free Survival; Liver Neoplasms
PubMed: 38087278
DOI: 10.1186/s12885-023-11711-7