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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 -
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 -
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 -
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 -
Transplantation Reviews (Orlando, Fla.) Jul 2023Post-hepatectomy liver failure is a severe complication after major liver resection and is associated with a high mortality rate. Nevertheless, there is no effective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Post-hepatectomy liver failure is a severe complication after major liver resection and is associated with a high mortality rate. Nevertheless, there is no effective treatment for severe liver failure. In such a setting, rescue liver transplantation (LT) is used only in extraordinary cases with unclear results. This systematic review aims to define indication of LT in post-hepatectomy liver failure and post-LT outcomes, in terms of patient and disease-free survivals, to assess the procedure's feasibility and effectiveness.
METHODS
A systematic review of all English language full-text articles published until September 2022 was conducted. Inclusion criteria were articles describing patients undergoing LT for post-hepatectomy liver failure after liver resection, which specified at least one outcome of interest regarding patient/graft survival, postoperative complications, tumour recurrence and cause of death. A pseudo-individual participant data meta-analysis was performed to analyse data. Study quality was assessed with MINORS system. PROSPERO CRD42022349358.
RESULTS
Postoperative complication rate was 53.6%. All patients transplanted for benign indications survived. For malignant tumours, 1-, 3- and 5-year overall survival was 94.7%, 82.1% and 74.6%, respectively. The causes of death were tumour recurrence in 83.3% of cases and infection-related in 16.7% of LT recipients. At Cox regression, being transplanted for unconventional malignant indications (colorectal liver metastasis, cholangiocarcinoma) was a risk factor for death HR = 8.93 (95%CI = 1.04-76.63; P-value = 0.046). Disease-free survival differs according to different malignant tumours (P-value = 0.045).
CONCLUSIONS
Post-hepatectomy liver failure is an emergent indication for rescue LT, but it is not universally accepted. In selected patients, LT can be a life-saving procedure with low short-term risks. However, special attention must be given to long-term oncological prognosis before proceeding with rescue LT in an urgent setting, considering the severity of liver malignancy, organ scarcity, the country's organ allocation policies and the resource of living-related donation.
Topics: Humans; Liver Transplantation; Neoplasm Recurrence, Local; Hepatectomy; Liver Neoplasms; Treatment Outcome; Risk Factors; Liver Failure, Acute; Liver Failure
PubMed: 37356212
DOI: 10.1016/j.trre.2023.100773 -
Critical Reviews in Oncology/hematology Apr 2024The effect of calorie restriction, fasting, and ketogenic diets on the treatment of liver cancer remains uncertain. Therefore, we conducted a systematic review to... (Meta-Analysis)
Meta-Analysis Review
The effect of calorie restriction, fasting, and ketogenic diets on the treatment of liver cancer remains uncertain. Therefore, we conducted a systematic review to evaluate the effect of restrictive diets on the development and progression of liver cancer in animal models. We did a meta-analysis using the Cochrane Collaboration's Review Manager software, with the random effects model and the inverse variance technique. We examined 19 studies that were conducted between 1983 and 2020. Of these, 63.2% investigated calorie restriction, 21.0% experimented with a ketogenic diet, and 15.8% investigated the effects of fasting. The intervention lasted anything from 48 h to 221 weeks. Results showed that restrictive diets may reduce tumor incidence and progression, with a significant reduction in the risk of liver cancer development. Thereby, our results suggest that putting limits on what you eat may help treat liver cancer in more ways than one.
Topics: Animals; Humans; Diet, Ketogenic; Caloric Restriction; Fasting; Liver Neoplasms
PubMed: 38341120
DOI: 10.1016/j.critrevonc.2024.104264 -
Clinical Journal of Sport Medicine :... Jan 2021Liver cancer is the second most common cause of death from cancer. Physical activity (PA) was found to be associated with lower risks of several types of cancer.... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Liver cancer is the second most common cause of death from cancer. Physical activity (PA) was found to be associated with lower risks of several types of cancer. However, the association between PA and the risk of liver cancer is still inconclusive. This systematic review and meta-analysis was aiming to summarize the association between PA and liver cancer risk.
METHODS
Literatures related were identified by searching PubMed, EMBASE, and Chinese Biomedical literature database from 1965 to 2017 without language limitation. Meta-analyses were performed using random effect model.
RESULTS
A total of 5 cohort studies involving 2 513 975 subjects were identified. The pooled relative risk of leisure-time PA with liver cancer risk was 0.92 [95% confidence interval (CI), 0.84-1.01]. There is no significant association between leisure-time PA and liver cancer risk. However, leisure-time PA significantly reduced liver cancer risk in never smokers. The pooled hazard ratio of daily total PA with liver cancer risk was 0.75 (95% CI, 0.66-0.86).
CONCLUSIONS
Daily total PA significantly reduces liver cancer risk, whereas leisure-time PA significantly reduces liver cancer risk only in never smokers.
Topics: Exercise; Humans; Liver Neoplasms; Non-Smokers; Risk Factors
PubMed: 30371534
DOI: 10.1097/JSM.0000000000000689 -
HPB : the Official Journal of the... Jan 2015Search and review of available literature were made to define the indications for and timing of liver transplantation for neuroendocrine tumour (NET) liver metastases. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Search and review of available literature were made to define the indications for and timing of liver transplantation for neuroendocrine tumour (NET) liver metastases.
METHODS
Electronic bibliographical databases were searched. Prospective and retrospective cohort studies and case-controlled studies were used for qualitative and quantitative synthesis of the systematic review. Reports of patients with liver transplantation alone for NET liver metastases of any origin or combined with resection of extrahepatic tumour deposits were recruited.
RESULTS
The number of patients who have undergone liver transplantation for NET liver metastases is 706. The post-transplant 5-year survival rate from the time of diagnosis was approximately 70%. NET patients with metastases confined to the liver and not poorly differentiated are favourable candidates for liver transplantation. Selection of patients based on evolution of tumours over 6 months is not recommended.
CONCLUSION
Non-resectable NET liver metastasis resistant to medical treatment and confined to the liver is an accepted indication for liver transplantation.
Topics: Humans; Liver Neoplasms; Liver Transplantation; Neuroendocrine Tumors; Patient Selection; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 24992381
DOI: 10.1111/hpb.12308