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The Lancet. Oncology Apr 2022The clinical presentation and outcomes of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma are unclear when compared with hepatocellular... (Meta-Analysis)
Meta-Analysis
Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis.
BACKGROUND
The clinical presentation and outcomes of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma are unclear when compared with hepatocellular carcinoma due to other causes. We aimed to establish the prevalence, clinical features, surveillance rates, treatment allocation, and outcomes of NAFLD-related hepatocellular carcinoma.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE and Embase from inception until Jan 17, 2022, for articles in English that compared clinical features, and outcomes of NAFLD-related hepatocellular carcinoma versus hepatocellular carcinoma due to other causes. We included cross-sectional and longitudinal observational studies and excluded paediatric studies. Study-level data were extracted from the published reports. The primary outcomes were (1) the proportion of hepatocellular carcinoma secondary to NAFLD, (2) comparison of patient and tumour characteristics of NAFLD-related hepatocellular carcinoma versus other causes, and (3) comparison of surveillance, treatment allocation, and overall and disease-free survival outcomes of NAFLD-related versus non-NAFLD-related hepatocellular carcinoma. We analysed proportional data using a generalised linear mixed model. Pairwise meta-analysis was done to obtain odds ratio (OR) or mean difference, comparing NAFLD-related with non-NAFLD-related hepatocellular carcinoma. We evaluated survival outcomes using pooled analysis of hazard ratios.
FINDINGS
Of 3631 records identified, 61 studies (done between January, 1980, and May, 2021; 94 636 patients) met inclusion criteria. Overall, the proportion of hepatocellular carcinoma cases secondary to NAFLD was 15·1% (95% CI 11·9-18·9). Patients with NAFLD-related hepatocellular carcinoma were older (p<0·0001), had higher BMI (p<0·0001), and were more likely to present with metabolic comorbidities (diabetes [p<0·0001], hypertension [p<0·0001], and hyperlipidaemia [p<0·0001]) or cardiovascular disease at presentation (p=0·0055) than patients with hepatocellular carcinoma due to other causes. They were also more likely to be non-cirrhotic (38·5%, 27·9-50·2 vs 14·6%, 8·7-23·4 for hepatocellular carcinoma due to other causes; p<0·0001). Patients with NAFLD-related hepatocellular carcinoma had larger tumour diameters (p=0·0087), were more likely to have uninodular lesions (p=0·0003), and had similar odds of Barcelona Clinic Liver Cancer stages, TNM stages, alpha fetoprotein concentration, and Eastern Cooperative Oncology Group (ECOG) performance status to patients with non-NAFLD-related hepatocellular carcinoma. A lower proportion of patients with NAFLD-related hepatocellular carcinoma underwent surveillance (32·8%, 12·0-63·7) than did patients with hepatocellular carcinoma due to other causes (55·7%, 24·0-83·3; p<0·0001). There were no significant differences in treatment allocation (curative therapy, palliative therapy, and best supportive care) between patients with NAFLD-related hepatocellular carcinoma and those with hepatocellular carcinoma due to other causes. Overall survival did not differ between the two groups (hazard ratio 1·05, 95% CI 0·92-1·20, p=0·43), but disease-free survival was longer for patients with NAFLD-related hepatocellular carcinoma (0·79, 0·63-0·99; p=0·044). There was substantial heterogeneity in most analyses (I>75%), and all articles had low-to-moderate risk of bias.
INTERPRETATION
NAFLD-related hepatocellular carcinoma is associated with a higher proportion of patients without cirrhosis and lower surveillance rates than hepatocellular carcinoma due to other causes. Surveillance strategies should be developed for patients with NAFLD without cirrhosis who are at high risk of developing hepatocellular carcinoma.
FUNDING
None.
Topics: Carcinoma, Hepatocellular; Child; Cross-Sectional Studies; Humans; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease
PubMed: 35255263
DOI: 10.1016/S1470-2045(22)00078-X -
Alimentary Pharmacology & Therapeutics Oct 2021Advances in imaging technology have the potential to transform the early diagnosis and treatment of hepatocellular carcinoma (HCC) through quantitative image analysis.... (Review)
Review
BACKGROUND
Advances in imaging technology have the potential to transform the early diagnosis and treatment of hepatocellular carcinoma (HCC) through quantitative image analysis. Computational "radiomic" techniques extract biomarker information from images which can be used to improve diagnosis and predict tumour biology.
AIMS
To perform a systematic review on radiomic features in HCC diagnosis and prognosis, with a focus on reporting metrics and methodologic standardisation.
METHODS
We performed a systematic review of all full-text articles published from inception through December 1, 2019. Standardised data extraction and quality assessment metrics were applied to all studies.
RESULTS
A total of 54 studies were included for analysis. Radiomic features demonstrated good discriminatory performance to differentiate HCC from other solid lesions (c-statistics 0.66-0.95), and to predict microvascular invasion (c-statistic 0.76-0.92), early recurrence after hepatectomy (c-statistics 0.71-0.86), and prognosis after locoregional or systemic therapies (c-statistics 0.74-0.81). Common stratifying features for diagnostic and prognostic radiomic tools included analyses of imaging skewness, analysis of the peritumoural region, and feature extraction from the arterial imaging phase. The overall quality of the included studies was low, with common deficiencies in both internal and external validation, standardised imaging segmentation, and lack of comparison to a gold standard.
CONCLUSIONS
Quantitative image analysis demonstrates promise as a non-invasive biomarker to improve HCC diagnosis and management. However, standardisation of protocols and outcome measurement, sharing of algorithms and analytic methods, and external validation are necessary prior to widespread application of radiomics to HCC diagnosis and prognosis in clinical practice.
Topics: Carcinoma, Hepatocellular; Hepatectomy; Humans; Liver Neoplasms; Prognosis; Retrospective Studies
PubMed: 34390014
DOI: 10.1111/apt.16563 -
Journal of Gastrointestinal Surgery :... Sep 2022Hepatic hemangiomas (HHs) are benign liver lesions often discovered incidentally on imaging for various unrelated pathologies. We herein review the etiology,... (Review)
Review
BACKGROUND
Hepatic hemangiomas (HHs) are benign liver lesions often discovered incidentally on imaging for various unrelated pathologies. We herein review the etiology, classification, diagnostic imaging, and management of HHs.
METHODS
A comprehensive systematic review was performed utilizing MEDLINE/PubMed and Web of Science databases, with the end of search date being March 1, 2022, regarding HH diagnosis, imaging, and management.
RESULTS
HHs can be broadly classified as capillary hemangiomas or cavernous hemangiomas. While the exact pathophysiology related to the development of HHs remains largely unknown, hormone exposure has been postulated to cause HH growth. HHs appear homogenously hyperechoic on US with distinct margins and posterior acoustic enhancement. While cavernous hemangiomas appear as well-defined hypodense lesions on pre-contrast CT images with the same density as the vasculature, one of the most reliable imaging features for diagnosing cavernous hemangiomas is high signal intensity on T2 weighted images. While most HHs are asymptomatic, some patients can present with pain or compressive symptoms with bleeding/rupture being very rare. Kasabach-Merritt syndrome is a rare but life-threatening condition associated with thrombocytopenia and microangiopathic hemolytic anemia. When HHs are symptomatic or in the setting of Kasabach Merritt syndrome, surgery is indicated. Enucleation is an attractive surgical option for HH as it spares normal liver tissue. Most patients experience symptom relief following surgical resection.
CONCLUSION
HHs are very common benign liver lesions. High-quality imaging is imperative to distinguish HHs from other liver lesions. Surgery is generally reserved for patients who present with symptoms such as pain, obstruction, or rarely Kasabach-Merritt syndrome. Surgery can involve either formal resection or, in most instances, simple enucleation. Patients generally have good outcomes following surgery with resolution of their symptoms.
Topics: Hemangioma; Hemangioma, Cavernous; Hormones; Humans; Kasabach-Merritt Syndrome; Liver Neoplasms; Pain
PubMed: 35705835
DOI: 10.1007/s11605-022-05382-1 -
Practical Radiation Oncology 2022This guideline provides evidence-based recommendations for the indications and technique-dose of external beam radiation therapy (EBRT) in hepatocellular carcinoma (HCC)...
PURPOSE
This guideline provides evidence-based recommendations for the indications and technique-dose of external beam radiation therapy (EBRT) in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC).
METHODS
The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the indications, techniques, and outcomes of EBRT in HCC and IHC. This guideline is intended to cover the definitive, consolidative, salvage, preoperative (including bridge to transplant), and adjuvant settings as well as palliative EBRT for symptomatic primary lesions. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.
RESULTS
Strong recommendations are made for using EBRT as a potential first-line treatment in patients with liver-confined HCC who are not candidates for curative therapy, as consolidative therapy after incomplete response to liver-directed therapies, and as a salvage option for local recurrences. The guideline conditionally recommends EBRT for patients with liver-confined multifocal or unresectable HCC or those with macrovascular invasion, sequenced with systemic or catheter-based therapies. Palliative EBRT is conditionally recommended for symptomatic primary HCC and/or macrovascular tumor thrombi. EBRT is conditionally recommended as a bridge to transplant or before surgery in carefully selected patients. For patients with unresectable IHC, consolidative EBRT with or without chemotherapy should be considered, typically after systemic therapy. Adjuvant EBRT is conditionally recommended for resected IHC with high-risk features. Selection of dose-fractionation regimen and technique should be based on disease extent, disease location, underlying liver function, and available technologies.
CONCLUSIONS
The task force has proposed recommendations to inform best clinical practices on the use of EBRT for HCC and IHC with strong emphasis on multidisciplinary care. Future studies should focus on further defining the role of EBRT in the context of liver-directed and systemic therapies and refining optimal regimens and techniques.
Topics: Carcinoma, Hepatocellular; Consensus; Dose Fractionation, Radiation; Humans; Liver Neoplasms; Radiation Oncology
PubMed: 34688956
DOI: 10.1016/j.prro.2021.09.004 -
Gastroenterology Sep 2021Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a rapidly changing landscape of treatments. In the past 20 years, numerous randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a rapidly changing landscape of treatments. In the past 20 years, numerous randomized controlled trials (RCTs) have aimed at improving outcomes across disease stages. We aimed to analyze the current evidence and identify potential factors influencing response to therapies.
METHODS
We conducted a systematic review of phase III RCTs (2002-2020) across disease stages. A meta-analysis was designed to examine the relationship between etiology and outcome after systemic therapies with either tyrosine-kinase inhibitor (TKI)/antiangiogenic or immune checkpoint inhibitor (ICI) therapy.
RESULTS
Out of 10,100 studies identified, 76 were phase III RCTs. Among them, a rigorous screening algorithm identified 49 with high quality including a total of 22,113 patients undergoing adjuvant (n = 7) and primary treatment for early (n = 2), intermediate (n = 7), and advanced (first-line, n = 21; second-line, n = 12) stages of disease. Nine of these trials were positive, 6 treatments have been adopted in guidelines (sorafenib [2 RCTs], lenvatinib, atezolizumab+bevacizumab, regorafenib, cabozantinib and ramucirumab), but 2 were not (adjuvant CIK cells and sorafenib plus hepatic arterial infusion with FOLFOX). Meta-analysis of 8 trials including 3739 patients revealed ICI therapy to be significantly more effective in patients with viral hepatitis compared with nonviral-related HCC, whereas no differences related to etiology were observed in patients treated with TKI/anti-vascular endothelial growth factor.
CONCLUSIONS
Among 49 high-quality RCTs conducted in HCC during 2002-2020, 9 resulted in positive results. A meta-analysis of systemic therapies suggests that immunotherapies may be more effective in viral etiologies.
Topics: Ablation Techniques; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Disease Progression; Evidence-Based Medicine; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Liver Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Progression-Free Survival; Radiopharmaceuticals; Randomized Controlled Trials as Topic; Time Factors
PubMed: 34126063
DOI: 10.1053/j.gastro.2021.06.008 -
Annals of Surgery Apr 2021To compare the oncologic outcomes of liver resection (LR) and local ablation therapies for HCC. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the oncologic outcomes of liver resection (LR) and local ablation therapies for HCC.
SUMMARY OF BACKGROUND DATA
Although several studies have compared LR and local ablation therapies, the optimal treatment of choice for HCC within the Milan criteria remains controversial.
METHODS
We systemically searched the MEDLINE, Embase, and Cochrane Library databases for randomized control trials (RCTs) and matched nonrandomized trials (NRTs) that compared LR and local ablation therapies for HCC within the Milan criteria. The primary outcome was overall survival (OS). Secondary outcomes were recurrence free survival (RFS) and recurrence pattern.
RESULTS
A total of 7 RCTs and 18 matched NRTs, involving 2865 patients in the LR group and 2764 patients in the local ablation therapy group [RFA, MWA, RFA plus trans-arterial chemoembolization (TACE)], were included. Although there was no significant difference in OS between LR and RFA, LR showed a significantly better 5-year RFS than RFA in the analysis of RCTs (hazards ratio: 0.75; 95% confidence interval: 0.62-0.92; P = 0.006). The RFA group showed a significantly higher local recurrence than the LR group in both analyses of RCTs and NRTs. Additionally, the LR group showed better OS and RFS than the MWA or RFA plus TACE groups.
CONCLUSION
Our meta-analysis showed that LR was superior to RFA in terms of RFS and incidence of local recurrence. Moreover, LR showed better oncologic outcomes than MWA or RFA plus TACE.
Topics: Carcinoma, Hepatocellular; Hepatectomy; Humans; Liver; Liver Neoplasms; Radiofrequency Ablation; Treatment Outcome
PubMed: 33074898
DOI: 10.1097/SLA.0000000000004350 -
Journal of Hepatology Jul 2022There is controversy regarding the overall value of hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis given the lack of data from... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
There is controversy regarding the overall value of hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis given the lack of data from randomized-controlled trials. To address this issue, we conducted a systematic review and meta-analysis of cohort studies evaluating the benefits and harms of HCC surveillance in patients with cirrhosis.
METHODS
We performed a search of the Medline and EMBASE databases and national meeting abstracts from January 2014 through July 2020 for studies reporting early-stage HCC detection, curative treatment receipt, or overall survival, stratified by HCC surveillance status, among patients with cirrhosis. Pooled risk ratios (RRs) and hazard ratios, according to HCC surveillance status, were calculated for each outcome using the DerSimonian and Laird method for random effects models.
RESULTS
We identified 59 studies including 145,396 patients with HCC, which was detected by surveillance in 41,052 (28.2%) cases. HCC surveillance was associated with improved early-stage detection (RR 1.86, 95% CI 1.73-1.98; I = 82%), curative treatment receipt (RR 1.83, 95% CI 1.69-1.97; I = 75%), and overall survival (hazard ratio 0.67, 95% CI 0.61-0.72; I = 78%) after adjusting for lead-time bias; however, there was notable heterogeneity in all pooled estimates. Four studies examined surveillance-related physical harms due to false positive or indeterminate surveillance results, but no studies examined potential financial or psychological harms. The proportion of patients experiencing surveillance-related physical harms ranged from 8.8% to 27.5% across studies, although most harms were mild in severity.
CONCLUSION
HCC surveillance is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there was heterogeneity in pooled estimates. Available data suggest HCC surveillance is of high value in patients with cirrhosis, although continued rigorous studies evaluating benefits and harms are still needed.
LAY SUMMARY
There has been ongoing debate about the overall value of hepatocellular carcinoma (HCC) screening in patients with cirrhosis given the lack of data from randomized-controlled trials. In a systematic review of contemporary cohort studies, we found that HCC screening is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there were fewer data quantifying potential screening-related harms. Available data suggest HCC screening is of high value in patients with cirrhosis, although continued studies evaluating benefits and harms are still needed.
Topics: Carcinoma, Hepatocellular; Early Diagnosis; Humans; Liver Cirrhosis; Liver Neoplasms; Mass Screening
PubMed: 35139400
DOI: 10.1016/j.jhep.2022.01.023 -
Journal of Environmental Sciences... Apr 2023Air pollution has previously been linked to several adverse health outcomes, but the potential association between air pollution and liver cancer remains unclear. We... (Review)
Review
Air pollution has previously been linked to several adverse health outcomes, but the potential association between air pollution and liver cancer remains unclear. We searched PubMed, EMBASE, and Web of Science from inception to 10 October 2021, and manually reviewed the references of relevant papers to further identify any related literature investigating possible associations between air pollution and liver cancer. Risk estimates values were represented by statistical associations based on quantitative analyses. A total of 13 cohort studies obtained from 11 articles were included, with 10,961,717 participants. PM was the most frequently examined pollutant (included in 11 studies), followed by NO and NO (included in 6 studies), and fewer studies focused on other pollutants (PM, PM, PM, O, and BC). In all the 16 associations for liver cancer mortality, 14 associations reported the effect of PM on liver cancer mortality. Eight associations on PM were significant, showing a suggestive association between PM and liver cancer mortality. Among 24 associations shown by risk estimates for liver cancer incidence, most associations were not statistically significant. For other air pollutants, no positive associations were presented in these studies. PM was the most frequently examined pollutant, followed by NO and NO, and fewer studies focused on other pollutants. PM was associated with liver cancer mortality, but there was no association for other air pollutants. Future research should use advanced statistical methods to further assess the impact of multiple air pollutants on liver cancer in the changing socio-environmental context.
Topics: Humans; Air Pollution; Air Pollutants; Liver Neoplasms; Environmental Pollutants
PubMed: 36503807
DOI: 10.1016/j.jes.2022.05.037 -
Cell Proliferation Oct 2023The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical... (Review)
Review
The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical management of liver metastases is challenging because of their strong heterogeneity, rapid progression, and poor prognosis. Now, exosomes, small membrane vesicles that are 40-160 nm in size, are released by tumour cells, namely, tumour-derived exosomes (TDEs), and are being increasingly studied because they can retain the original characteristics of tumour cells. Cell-cell communication via TDEs is pivotal for liver pre-metastatic niche (PMN) formation and liver metastasis; thus, TDEs can provide a theoretical basis to intensively study the potential mechanisms of liver metastasis and new insights into the diagnosis and treatment of liver metastasis. Here, we systematically review current research progress about the roles and possible regulatory mechanisms of TDE cargos in liver metastasis, focusing on the functions of TDEs in liver PMN formation. In addition, we discuss the clinical utility of TDEs in liver metastasis, including TDEs as potential biomarkers, and therapeutic approaches for future research reference in this field.
Topics: Humans; Exosomes; Liver Neoplasms; Cell Communication; Pancreas; Biomarkers, Tumor; Tumor Microenvironment; Neoplasm Metastasis
PubMed: 36941028
DOI: 10.1111/cpr.13452 -
Public Health Nutrition Dec 2023This systematic review aimed to investigate the association between dietary inflammatory potential and liver cancer to provide evidence regarding scientific dietary... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review aimed to investigate the association between dietary inflammatory potential and liver cancer to provide evidence regarding scientific dietary health education.
DESIGN
Systematic review and meta-analysis.
SETTING
A comprehensive literature review was conducted to identify case-control or cohort studies that involved dietary inflammation index (DII)/empirical dietary inflammation pattern (EDIP) and liver cancer in PubMed, EMBASE, Cochrane, and Web of Science databases. Using a combination of DII/EDIP and liver cancer as the search terms, the associations between DII/EDIP and liver cancer were then assessed.
PARTICIPANTS
Three case-control studies and two cohort studies were brought into the meta-analysis, with 225 713 enrolled participants.
RESULTS
Meta-analysis of categorical variables showed that DII/EDIP in the highest category increased the risk of liver cancer compared to DII/EDIP in the lowest category (relative risk (RR) = 2·35; 95 % CI 1·77, 3·13; = 0·000) and with low heterogeneity across studies (I = 40·8 %, = 0·119). Meta-analysis of continuous variables showed that significant positive association between liver cancer and DII/EDIP scores (RR = 1·24; 95 % CI 1·09, 1·40; = 0·001), and no heterogeneity (I² = 0·0 %, = 0·471). Stratified according to the study design, there was a significant positive association between liver cancer and DII/EDIP scores in both cohort studies (RR = 2·16; 95 % CI 1·51, 3·07; = 0·000) and case-control studies (RR = 2·75; 95 % CI 1·71, 4·41; = 0·000).
CONCLUSION
The higher the DII/EDIP score, the higher the risk of liver cancer. This finding may have prominent implications for the general population.
Topics: Humans; Risk Factors; Diet; Inflammation; Liver Neoplasms; Dietary Patterns
PubMed: 37990536
DOI: 10.1017/S1368980023002574