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Experimental & Molecular Medicine Dec 2020Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and a leading cause of cancer-related deaths worldwide. Ninety percent of HCC cases arise from... (Review)
Review
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and a leading cause of cancer-related deaths worldwide. Ninety percent of HCC cases arise from cirrhosis, during which liver cells undergo chronic cycles of necrosis and regeneration. The complex genomic landscape of HCC has been extensively investigated to draw correlations between recurrently mutated pathways and patient prognosis. However, our limited success with targeted therapy shows that knowing the presence of somatic mutations alone is insufficient for us to gauge the full spectrum of their functional consequences in the context of tumor evolution. In addition, the current molecular classification of HCC offers little information on the relationship between the molecular features and immunological properties of HCC tumors and their immune microenvironment. This review introduces current challenges and advancements made in HCC surveillance, diagnosis, and treatment. We also discuss the suite of HCC-associated genetic changes and describe recent studies that provide evidence for an evolving functional model and its implications for understanding and targeting HCC progression.
Topics: Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular; Clinical Decision-Making; Disease Management; Disease Susceptibility; Humans; Liver Neoplasms; Molecular Diagnostic Techniques; Prognosis; Tumor Microenvironment
PubMed: 33268834
DOI: 10.1038/s12276-020-00527-1 -
Bioscience Trends Mar 2022Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer-related mortality worldwide. This review is an updated version... (Review)
Review
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer-related mortality worldwide. This review is an updated version that summarizes comprehensive guidelines published from January 2001 to January 2022 worldwide with a focus on the clinical management of HCC. The electronic databases MEDLINE, the Chinese SinoMed, and the Japanese CiNii were systematically searched. A total of 22 characteristic guidelines for HCC management were ultimately included, including 1 international guideline, 11 guidelines from Asia, 5 from Europe, 4 from the America, and 1 from Australia. If guidelines were published in multiple versions, the most recent update was included, and surveillance, diagnosis, and treatment were compared. The composition of and recommendations in current guidelines on HCC varied, so these guidelines were regrouped and diagnostic and treatment algorithms were summarized graphically to provide the latest information to clinicians. The diagnostic criteria were grouped into 2 categories: a "Size-based pathway" and a "Non-size-based pathway". The treatment criteria were summarized according to different treatment algorithms, and mainstream treatment options were reviewed. Findings from comparison of current guidelines might help target and concentrate efforts to improve the clinical management of HCC. However, further studies are needed to improve the management and outcomes of HCC. More straightforward or refined guidelines would help guide doctors to make better decisions in the treatment of HCC in the future.
Topics: Algorithms; Australia; Carcinoma, Hepatocellular; Humans; Liver Neoplasms
PubMed: 35197399
DOI: 10.5582/bst.2022.01061 -
Clinical and Translational Medicine Jul 2023The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics of the tumour microenvironment (TME). Recent studies have confirmed the...
BACKGROUND
The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics of the tumour microenvironment (TME). Recent studies have confirmed the presence and potential influence of the microbiome in TME on cancer progression. Elucidating the relationship between microbes in the TME and cancer could provide valuable insights into novel diagnostic markers and therapeutic strategies for HCC and thus warrants a closer investigation of the role of intratumoural microbiome in the HCC TME.
METHODS
We determined the presence of intratumoural microbiome using fluorescence in situ hybridisation, and explored the microbial community profiles in the HCC TME in paired tumour and adjacent normal tissues using 16S rDNA sequencing. Microbial signatures were characterised in the paired group, and their correlation with clinical characteristics was further investigated. We clustered the microbial signatures of tumour tissues by hepatotypes, and further analysis was performed to elucidate the independent prognostic value of the hepatotypes.
RESULTS
This study revealed that microbial profiles and community networks differed notably between tumours and adjacent normal tissues. Proteobacteria and Actinobacteria were the most abundant phyla in the HCC TME. The TME microbial profiles also revealed heterogeneities between individuals and between multiple tumour lesions. Clustering of the microbial profiles into two hepatotypes revealed different microbial network patterns. Additionally, the hepatotypes were revealed to be independent prognostic factors in patients with resected HCC.
CONCLUSIONS
Our study illuminates the microbial profiles in the TME of HCC and presents the hepatotype as a potential independent biomarker for the prognostic prediction of HCC after surgery.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Microbiota; Tumor Microenvironment
PubMed: 37462602
DOI: 10.1002/ctm2.1331 -
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 -
Analytical Cellular Pathology... 2020
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Prognosis
PubMed: 32089989
DOI: 10.1155/2020/8157406 -
Clinical and Molecular Hepatology Oct 2022Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic...
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Topics: Humans; Male; Carcinoma, Hepatocellular; Hepatitis B, Chronic; Liver Neoplasms; Prevalence; Republic of Korea
PubMed: 36263666
DOI: 10.3350/cmh.2022.0294 -
BioMed Research International 2014
Topics: Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Disease Progression; Humans; Liver Neoplasms
PubMed: 25028663
DOI: 10.1155/2014/706142 -
Journal of Hepatology Apr 2012
Topics: Adolescent; Aged; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Young Adult
PubMed: 22424438
DOI: 10.1016/j.jhep.2011.12.001 -
International Journal of Molecular... Sep 2022Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide [...].
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide [...].
Topics: Carcinoma, Hepatocellular; Humans; Immunotherapy; Liver Neoplasms
PubMed: 36232663
DOI: 10.3390/ijms231911363 -
Annals of Oncology : Official Journal... Jun 2021
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms
PubMed: 33716105
DOI: 10.1016/j.annonc.2021.02.014