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European Journal of Cancer (Oxford,... May 2023Adiposity is associated with an increased risk of primary liver cancer (PLC). As the most commonly used indicator of adiposity, the body mass index (BMI) has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Adiposity is associated with an increased risk of primary liver cancer (PLC). As the most commonly used indicator of adiposity, the body mass index (BMI) has been questioned for its limitations in reflecting visceral fat. This study aimed to investigate the role of different anthropometric indicators in identifying the risk of PLC by accounting for potential non-linear associations.
METHODS
Systematic searches were conducted in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, and CNKI databases. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship was assessed using a restricted cubic spline model.
RESULTS
Sixty-nine studies involving more than 30 million participants were included in the final analysis. Regardless of the indicator used, adiposity was strongly associated with an increased risk of PLC. When comparing the HRs per 1-standard deviation increment across indicators of adiposity, the association was strongest for waist-to-height ratio (WHtR) (HR = 1.39), followed by waist-to-hip ratio (WHR) (HR = 1.22), BMI (HR = 1.13), waist circumference (WC) (HR = 1.12), and hip circumference (HC) (HR = 1.12). A strong non-linear association was observed between each anthropometric parameter and the risk of PLC, regardless of whether the original or decentralised value was used. The positive association between WC and PLC risk remained substantial after adjusting for BMI. The incidence of PLC was higher with central adiposity (52.89 per 100,000 person-years, 95% CI = 50.33-55.44) than general adiposity (39.01 per 100,000 person-years, 95% CI = 37.26-40.75).
CONCLUSION
Central adiposity seems to contribute more to the development of PLC than general adiposity. A larger WC, independent of BMI, was strongly associated with the risk of PLC and might be a more promising predictive indicator than BMI.
Topics: Humans; Adiposity; Risk Factors; Obesity; Waist Circumference; Body Mass Index; Liver Neoplasms
PubMed: 36996625
DOI: 10.1016/j.ejca.2023.03.005 -
Alimentary Pharmacology & Therapeutics May 2024The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery.
METHODS
A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy.
RESULTS
A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis.
CONCLUSION
The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.
Topics: Child; Humans; Carcinoma, Hepatocellular; Incidence; Liver Neoplasms; Fontan Procedure; Liver Cirrhosis; Risk Factors
PubMed: 38497159
DOI: 10.1111/apt.17952 -
Clinical and Molecular Hepatology Apr 2024Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events.
METHODS
We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events.
RESULTS
19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05).
CONCLUSION
People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.
Topics: Adult; Humans; Middle Aged; Non-alcoholic Fatty Liver Disease; Incidence; Carcinoma, Hepatocellular; Metabolic Syndrome; Liver Neoplasms; Liver Cirrhosis; Fibrosis; Hypertension; Cardiovascular Diseases
PubMed: 38281814
DOI: 10.3350/cmh.2023.0485 -
Surgical Endoscopy Dec 2023Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as...
SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm.
BACKGROUND
Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies.
METHODS
A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations.
RESULTS
The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence).
CONCLUSION
Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Microwaves; Catheter Ablation; Treatment Outcome; Radiofrequency Ablation; Colorectal Neoplasms; Retrospective Studies
PubMed: 37957297
DOI: 10.1007/s00464-023-10468-1 -
International Journal of Colorectal... Apr 2023Combined resection of primary colorectal cancer and associated liver metastases is increasingly common. This study compares peri-operative and oncological outcomes... (Meta-Analysis)
Meta-Analysis
PURPOSE
Combined resection of primary colorectal cancer and associated liver metastases is increasingly common. This study compares peri-operative and oncological outcomes according to surgical approach.
METHODS
The study was registered with PROSPERO. A systematic search was performed for all comparative studies describing outcomes in patients that underwent laparoscopic versus open simultaneous resection of colorectal primary tumours and liver metastases. Data was extracted and analysed using a random effects model via Rev Man 5.3 RESULTS: Twenty studies were included with a total of 2168 patients. A laparoscopic approach was performed in 620 patients and an open approach in 872. There was no difference in the groups for BMI (mean difference: 0.04, 95% CI: 0.63-0.70, p = 0.91), number of difficult liver segments (mean difference: 0.64, 95% CI:0.33-1.23, p = 0.18) or major liver resections (mean difference: 0.96, 95% CI: 0.69-1.35, p = 0.83). There were fewer liver lesions per operation in the laparoscopic group (mean difference 0.46, 95% CI: 0.13-0.79, p = 0.007). Laparoscopic surgery was associated with shorter length of stay (p < 0.00001) and less overall postoperative complications (p = 0.0002). There were similar R0 resection rates (p = 0.15) but less disease recurrence in the laparoscopic group (mean difference: 0.57, 95% CI:0.44-0.75, p < 0.0001).
CONCLUSION
Synchronous laparoscopic resection of primary colorectal cancers and liver metastases is a feasible approach in selected patients and does not demonstrate inferior peri-operative or oncological outcomes.
Topics: Humans; Treatment Outcome; Neoplasm Recurrence, Local; Colorectal Neoplasms; Hepatectomy; Liver Neoplasms; Laparoscopy; Postoperative Complications; Length of Stay
PubMed: 37017766
DOI: 10.1007/s00384-023-04375-z -
United European Gastroenterology Journal Oct 2023Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension...
BACKGROUND/AIMS
Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension (PH)-related complications without worsening liver function, and increase overall survival. Data on the efficacy and safety of TIPS to treat PH complications in HCC patients, as well as the HCC treatment response, were evaluated.
METHODS
Studies reporting efficacy in controlling bleeding/ascites or response to HCC therapy, safety, and survival in patients with HCC and TIPS were searched systematically on PubMed and Embase. An extraction of articles using predefined data fields and quality indicators was used.
RESULTS
We selected 19 studies and found 937 patients treated for ascites/bleeding and 177 evaluating HCC treatment response. Over half were under 5 cm and solitary lesions, and most studies included tumours with portal vein thrombosis. Regarding PH studies, TIPS resolved bleeding/ascites in >60% of patients, more effective for bleeding. There were no lethal complications reported and procedural bleeding occurred in <5%. Hepatic encephalopathy occurred in 15%-30% within three months. In the HCC treatment-response studies, major complication rates were low with no mortality. In the studies that evaluated the response to transarterial chemoembolization, complete response rate of patients with TIPS varied from 16% to 75%. Liver transplantation rate varied from 8% to 80%, with >40% rate in half of the studies.
CONCLUSIONS
In the published studies, TIPS is effective in treating PH complications in patients with HCC. Prospective studies on TIPS placement in patients with HCC are urgently needed to evaluate the efficacy and safety of TIPS in this setting.
Topics: Humans; Carcinoma, Hepatocellular; Portasystemic Shunt, Transjugular Intrahepatic; Liver Neoplasms; Ascites; Prospective Studies; Esophageal and Gastric Varices; Treatment Outcome; Chemoembolization, Therapeutic; Hypertension, Portal
PubMed: 37736854
DOI: 10.1002/ueg2.12454 -
European Journal of Surgical Oncology :... Jul 2024Salvage liver transplantation (SLT) is an effective treatment option for recurrent hepatocellular carcinoma (rHCC) following primary curative treatment (CUR). However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Salvage liver transplantation (SLT) is an effective treatment option for recurrent hepatocellular carcinoma (rHCC) following primary curative treatment (CUR). However, its efficacy remains controversial compared to that of CURs, including repeat liver resection (RLR) and local ablation. This meta-analysis compared the efficacy and safety of these procedures.
METHODS
A systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases for studies investigating SLT and CUR was performed. Outcome data, including overall and disease-free survival, tumor response, and operative and postoperative outcomes, were independently extracted and analyzed by two authors using a standardized protocol.
RESULTS
Fifteen cohort studies comprising 508 and 2050 patients with rHCC, who underwent SLT or CUR, respectively, were included. SLT achieved significantly longer overall survival than both CUR (hazard ratio [HR]: 0.56, 95 % confidence interval [CI]: 0.45-0.68; I = 34.6 %, p = 0.105) and RLR (HR: 0.64, 95 % CI: 0.49-0.84; I = 0.0 %, p = 0.639). Similar significantly better survival benefits were observed compared with CUR (HR: 0.30, 95 % CI: 0.20-0.45; I = 51.1 %, p = 0.038) or RLR (HR: 0.31, 95 % CI: 0.18-0.56; I = 65.7 %, p = 0.005) regarding disease-free survival. However, SLT resulted in a longer operative duration and hospital stay, larger amount of blood loss, higher rate of transfusion and postoperative morbidity, and slightly higher postoperative mortality than CUR.
CONCLUSION
SLT was associated with better long-term survival than CUR or RLR in patients with rHCC after primary curative treatment.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local; Salvage Therapy; Hepatectomy; Survival Rate
PubMed: 38796968
DOI: 10.1016/j.ejso.2024.108427 -
EBioMedicine Jul 2023Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently...
BACKGROUND
Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA.
METHODS
We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance.
FINDINGS
We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort (n = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort (n = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928).
INTERPRETATION
This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP.
FUNDING
National Natural Science Foundation of China, and The National Key Basic Research Program (973 program).
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Cell-Free Nucleic Acids; Biomarkers, Tumor; ROC Curve; MicroRNAs
PubMed: 37315449
DOI: 10.1016/j.ebiom.2023.104645 -
Clinical Cancer Research : An Official... Aug 2022Because of the increased number of sequential treatments used for advanced hepatocellular carcinoma (HCC), there is a need for surrogate endpoints of overall survival... (Meta-Analysis)
Meta-Analysis
PURPOSE
Because of the increased number of sequential treatments used for advanced hepatocellular carcinoma (HCC), there is a need for surrogate endpoints of overall survival (OS). We analyze whether objective response (OR) is an independent predictor and surrogate endpoint of OS.
PATIENTS AND METHODS
A systematic review of randomized clinical trials (RCT) in advanced HCC published between 2010 and 2020 was conducted to explore OS surrogacy of OR by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST). In parallel, RCTs exploring the impact of OR on OS in a time-dependent multivariate analysis were integrated in a meta-analysis.
RESULTS
Of 65 RCTs identified in advanced HCC, we analyzed 34 studies including 14,056 patients that reported OS and OR by either RECIST (n = 23), mRECIST (n = 5), or both (n = 6). When exploring surrogacy, the trial-level correlation between OR odds ratio and OS HR was R = 0.677 by mRECIST and R = 0.532 by RECIST. Meta-analysis of five RCTs assessing predictors of survival in multivariate analysis found that patients with OR by mRECIST presented a pooled HR for OS of 0.44 (95% confidence interval, 0.27-0.70; P < 0.001) compared with nonresponders. Responses to atezolizumab-bevacizumab had a greater impact on OS than tyrosine kinase inhibitor responses.
CONCLUSIONS
OR-mRECIST is an independent predictor of OS in patients with advanced HCC. Although correlation of OR-mRECIST and OS is better than with OR-RECIST, the level of surrogacy is modest. Thus, it can be used as endpoint in proof-of-concept phase II trials, but the data do not support its use as a primary endpoint of phase III investigations assessing systemic therapies.
Topics: Antineoplastic Agents; Biomarkers; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Randomized Controlled Trials as Topic; Response Evaluation Criteria in Solid Tumors; Survival Analysis
PubMed: 34907081
DOI: 10.1158/1078-0432.CCR-21-3135 -
Liver International : Official Journal... Jun 2020The Liver Imaging Reporting and Data System (LI-RADS) category M (LR-M) was introduced to preserve the high specificity of LI-RADS algorithm for diagnosing... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The Liver Imaging Reporting and Data System (LI-RADS) category M (LR-M) was introduced to preserve the high specificity of LI-RADS algorithm for diagnosing hepatocellular carcinoma (HCC). We aimed to systematically determine the probability of the LR-M for HCC and non-HCC malignancy, and to determine the sources of heterogeneity between reported results.
METHODS
Original studies reporting the probability of LR-M for HCC and non-HCC malignancy on magnetic resonance imaging (MRI) were identified in MEDLINE and EMBASE. The meta-analytic pooled percentages of HCC and non-HCC in LR-M were calculated. Meta-regression analysis was performed to explore study heterogeneity. The meta-analytic frequency of each LR-M imaging feature was determined.
RESULTS
We found 10 studies reporting the diagnostic performance of LR-M (1819 lesions in 1631 patients), and six reporting the frequency of LR-M imaging features. The pooled percentages of HCC and non-HCC malignancy for LR-M were 28.2% (95% confidence interval [CI], 23.8%-33.1%; I = 83%) and 69.6% (95% CI, 64.6%-74.1%; I = 83%) respectively. The study type and MRI scanner field strength were significantly associated with study heterogeneity (P ≤ .04). Of the seven imaging features, rim arterial phase hyperenhancement showed the highest frequency in both non-HCC (48.9%; 95% CI, 43.0%-54.8%) and HCC groups (9.8%; 95% CI, 6.9%-13.6%).
CONCLUSIONS
The LR-M category most commonly included non-HCC malignancy but also included 28.2% of HCC. Substantial study heterogeneity was noted, and it was significantly associated with study type and MRI scanner field strength. In addition, the frequency of LR-M imaging features was variable.
Topics: Algorithms; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Retrospective Studies
PubMed: 32129541
DOI: 10.1111/liv.14420