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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 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 -
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 -
World Journal of Surgical Oncology Dec 2023In recent years, the capacity of tumor cells to maintain high levels of glycolysis, even in the presence of oxygen, has emerged as one of the main metabolic traits and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, the capacity of tumor cells to maintain high levels of glycolysis, even in the presence of oxygen, has emerged as one of the main metabolic traits and garnered considerable attention. The purpose of this meta-analysis is to investigate the prognostic value of glycolysis markers in liver cancer.
METHODS
PubMed, Embase, and Cochrane Library databases were searched for articles on glycolytic marker expression levels associated with the prognosis of liver cancer until April 2023. Stata SE14.0 was used to calculate the aggregate hazard ratios and 95% confidence intervals.
RESULTS
Thirty-five studies were included. The worse overall survival (OS) (P < 0.001), disease-free survival (DFS) (P = 0.001), recurrence-free survival (RFS) (P = 0.004), and time to recurrence (TTR) (P < 0.001) were significantly associated with elevated expression of glycolysis markers. Higher expression of PKM2 (P < 0.001), STMN1 (P = 0.002), MCT4 (P < 0.001), GLUT1 (P = 0.025), HK-2 (P < 0.001), and CA9 (P < 0.001) were significantly related to shorter OS. Increased levels of PKM2 (P < 0.001), CA9 (P = 0.005), and MCT4 (P < 0.001) were associated with worse DFS. Elevated PKM2 expression (P = 0.002) was also associated with poorer RFS in hepatocellular carcinoma patients. GLUT2 expression was not correlated with the prognosis of liver cancer (P = 0.134).
CONCLUSIONS
Elevated expression of glycolysis markers was associated with worse OS, DFS, RFS, and TTR in patients with liver cancer. Therefore, these glycolysis markers could serve as potential prognostic markers and therapeutic targets in liver cancer.
TRIAL REGISTRATION
PROSPERO registration: CRD42023469645.
Topics: Humans; Biomarkers, Tumor; Liver Neoplasms; Carcinoma, Hepatocellular; Prognosis; Glycolysis
PubMed: 38114977
DOI: 10.1186/s12957-023-03275-4 -
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 -
International Journal of Surgery... Sep 2023Despite retrospective studies comparing anatomical liver resection (AR) and non-anatomical liver resection (NAR), the efficacy and benefits of AR for hepatocellular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite retrospective studies comparing anatomical liver resection (AR) and non-anatomical liver resection (NAR), the efficacy and benefits of AR for hepatocellular carcinoma remain unclear.
MATERIALS AND METHODS
The authors systemically reviewed MEDLINE, Embase, and Cochrane Library for propensity score matched cohort studies that compared AR and NAR for hepatocellular carcinoma. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). Secondary outcomes were recurrence patterns and perioperative outcomes.
RESULTS
Overall, 22 propensity score matched studies (AR, n =2,496; NAR, n =2590) were included. AR including systemic segmentectomy was superior to NAR regarding the 3-year and 5-year OS. AR showed significantly better 1-year, 3-year, and 5-year RFS than NAR, with low local and multiple intrahepatic recurrence rates. In the subgroup analyses of tumour diameter less than or equal to 5 cm and tumours with microscopic spread, the RFS in the AR group was significantly better than that in the NAR group. Patients with cirrhotic liver in the AR group showed comparable 3-year and 5-year RFS with the NAR group. Postoperative overall complications were comparable between AR and NAR.
CONCLUSIONS
This meta-analysis demonstrated that AR showed better OS and RFS with a low local and multiple intra-hepatic recurrence rate than NAR, especially in patients with tumour diameter less than or equal to 5 cm and non-cirrhotic liver.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Hepatectomy; Propensity Score; Postoperative Complications; Neoplasm Recurrence, Local
PubMed: 37247010
DOI: 10.1097/JS9.0000000000000503 -
European Journal of Surgical Oncology :... Jul 2011To analyze surgical treatment of breast cancer liver metastases (BCLM) regarding selection criteria, outcome and prognostic parameters. (Review)
Review
AIM
To analyze surgical treatment of breast cancer liver metastases (BCLM) regarding selection criteria, outcome and prognostic parameters.
METHODS
We searched Embase and Medline for all studies published 1999-2010.
RESULTS
Resection was associated with a median survival (MOS) of 20-67 months and 5-year survival of 21-61%. Local ablation also had a favorable outcome; MOS was 30-60 months and 5-year survival 27-41%. Regarding selection, no specific limits regarding the number and size of BCLM can be given. Features of the primary breast cancer (BC) were not significant for the prognosis. Microscopically radical (R0) resection is a positive prognostic factor, while the effects of disease interval, hormone receptor status and response to preoperative chemotherapy were divergent. The presence of EHD had a negative effect on survival in some studies, but failed to have so in other studies.
CONCLUSIONS
Surgical therapy may benefit a subset of patients with BCLM. Resection may be indicated, if an RO-resection can be done with a low risk of mortality. Liver resection in the presence of extrahepatic disease remains controversial, while patients with BCLM and bone metastases could possibly be managed differently than other EHD.
Topics: Breast Neoplasms; Catheter Ablation; Female; Hepatectomy; Humans; Liver Neoplasms; Patient Selection; Prognosis
PubMed: 21605957
DOI: 10.1016/j.ejso.2011.04.013 -
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 -
World Journal of Surgery Nov 2021Colorectal liver metastases were historically considered a contraindication to liver transplantation, but dismal outcomes for those with metastatic colorectal cancer and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUNDS
Colorectal liver metastases were historically considered a contraindication to liver transplantation, but dismal outcomes for those with metastatic colorectal cancer and advancements in liver transplantation (LT) have led to a renewed interest in the topic. We aim to compare the current evidence for liver transplantation for non-resectable colorectal liver metastases (NRCLM) with the current standard treatment of palliative chemotherapy.
METHODS
A systematic review and meta-analysis of proportions was conducted following screening of MEDLINE, EMBASE, SCOPUS and CENTRAL for studies reporting liver transplantation for colorectal liver metastases. Post-operative outcomes measured included one-, three- and five-year survival, overall survival, disease-free survival and complication rate.
RESULTS
Three non-randomised studies met the inclusion criteria, reporting a total of 48 patients receiving LT for NRCLM. Survival at one-, three- and five-years was 83.3-100%, 58.3-80% and 50-80%, respectively, with no significant difference detected (p = 0.22, p = 0.48, p = 0.26). Disease-free survival was 35-56% with the most common site of recurrence being lung. Thirteen out of fourteen deaths were due to disease recurrence.
CONCLUSION
Although current evidence suggests a survival benefit conferred by LT in NRCLM compared to palliative chemotherapy, the ethical implications of organ availability and allocation demand rigorous justification. Concomitant improvements in the management of patients following liver resection and of palliative chemotherapy regimens is paramount.
Topics: Colorectal Neoplasms; Hepatectomy; Humans; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local
PubMed: 34322717
DOI: 10.1007/s00268-021-06248-4