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Lancet (London, England) Mar 2018Hepatocellular carcinoma appears frequently in patients with cirrhosis. Surveillance by biannual ultrasound is recommended for such patients because it allows diagnosis... (Review)
Review
Hepatocellular carcinoma appears frequently in patients with cirrhosis. Surveillance by biannual ultrasound is recommended for such patients because it allows diagnosis at an early stage, when effective therapies are feasible. The best candidates for resection are patients with a solitary tumour and preserved liver function. Liver transplantation benefits patients who are not good candidates for surgical resection, and the best candidates are those within Milan criteria (solitary tumour ≤5 cm or up to three nodules ≤3 cm). Image-guided ablation is the most frequently used therapeutic strategy, but its efficacy is limited by the size of the tumour and its localisation. Chemoembolisation has survival benefit in asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread. Finally, sorafenib, lenvatinib, which is non-inferior to sorafenib, and regorafenib increase survival and are the standard treatments in advanced hepatocellular carcinoma. This Seminar summarises the scientific evidence that supports the current recommendations for clinical practice, and discusses the areas in which more research is needed.
Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Combined Modality Therapy; Hepatectomy; Humans; Liver Neoplasms; Liver Transplantation
PubMed: 29307467
DOI: 10.1016/S0140-6736(18)30010-2 -
Advances in Cancer Research 2021Hepatocellular carcinoma (HCC), the primary malignancy of hepatocytes, is a diagnosis with bleak outcome. According to National Cancer Institute's SEER database, the... (Review)
Review
Hepatocellular carcinoma (HCC), the primary malignancy of hepatocytes, is a diagnosis with bleak outcome. According to National Cancer Institute's SEER database, the average five-year survival rate of HCC patients in the US is 19.6% but can be as low as 2.5% for advanced, metastatic disease. When diagnosed at early stages, it is treatable with locoregional treatments including surgical resection, Radio-Frequency Ablation, Trans-Arterial Chemoembolization or liver transplantation. However, HCC is usually diagnosed at advanced stages when the tumor is unresectable, making these treatments ineffective. In such instances, systemic therapy with tyrosine kinase inhibitors (TKIs) becomes the only viable option, even though it benefits only 30% of patients, provides only a modest (~3months) increase in overall survival and causes drug resistance within 6months. HCC, like many other cancers, is highly heterogeneous making a one-size fits all option problematic. The selection of liver transplantation, locoregional treatment, TKIs or immune checkpoint inhibitors as a treatment strategy depends on the disease stage and underlying condition(s). Additionally, patients with similar disease phenotype can have different molecular etiology making treatment responses different. Stratification of patients at the molecular level would facilitate development of the most effective treatment option. With the increase in efficiency and affordability of "omics"-level analysis, considerable effort has been expended in classifying HCC at the molecular, metabolic and immunologic levels. This review examines the results of these efforts and the ways they can be leveraged to develop targeted treatment options for HCC.
Topics: Animals; Carcinoma, Hepatocellular; Humans; Liver Neoplasms
PubMed: 33579421
DOI: 10.1016/bs.acr.2020.10.001 -
Nature Reviews. Gastroenterology &... Oct 2019Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C,... (Review)
Review
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease (particularly nonalcoholic fatty liver disease) and exposure to dietary toxins such as aflatoxins and aristolochic acid. All these risk factors are potentially preventable, highlighting the considerable potential of risk prevention for decreasing the global burden of HCC. HCC surveillance and early detection increase the chance of potentially curative treatment; however, HCC surveillance is substantially underutilized, even in countries with sufficient medical resources. Early-stage HCC can be treated curatively by local ablation, surgical resection or liver transplantation. Treatment selection depends on tumour characteristics, the severity of underlying liver dysfunction, age, other medical comorbidities, and available medical resources and local expertise. Catheter-based locoregional treatment is used in patients with intermediate-stage cancer. Kinase and immune checkpoint inhibitors have been shown to be effective treatment options in patients with advanced-stage HCC. Together, rational deployment of prevention, attainment of global goals for viral hepatitis eradication, and improvements in HCC surveillance and therapy hold promise for achieving a substantial reduction in the worldwide HCC burden within the next few decades.
Topics: Carcinoma, Hepatocellular; Global Health; Humans; Liver Neoplasms; Risk Factors
PubMed: 31439937
DOI: 10.1038/s41575-019-0186-y -
Cells Jun 2020Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. Thus, there is a constant search for improvement in screening, diagnosis, and... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. Thus, there is a constant search for improvement in screening, diagnosis, and treatment strategies to improve the prognosis of this malignancy. The identification of useful biomarkers for surveillance and early HCC diagnosis is still deficient, with available serum biomarkers showing low sensitivity and heterogeneous specificity despite different cut-off points, even when assessed longitudinally, or with a combination of serum biomarkers. In contrast, HCC biomarkers used for prognostic (when associated with clinical outcomes) or predictive purposes (when associated with treatment response) may have an increased clinical role in the near future. Furthermore, some serum biomarkers are already implicated as a treatment selection tool, whether to provide access to certain therapies or to assess clinical benefit after treatment. In the present review we will discuss the clinical utility and foreseen future of HCC biomarkers implicated in surveillance, diagnosis, prognosis, and post-treatment assessment.
Topics: Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular; Genomics; Humans; Liver Neoplasms; Neoplasm Staging; Prognosis; Treatment Outcome
PubMed: 32492896
DOI: 10.3390/cells9061370 -
World Journal of Gastroenterology Feb 2023Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative... (Review)
Review
Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Neoplasm Recurrence, Local; Hepatectomy; Risk Factors; Retrospective Studies
PubMed: 36925456
DOI: 10.3748/wjg.v29.i8.1243 -
Pathologica Jun 2021HCC incidence rates have been rising in the past 3 decades and by 2025 > 1 million individuals will be affected annually. High-throughput sequencing technologies led to... (Review)
Review
HCC incidence rates have been rising in the past 3 decades and by 2025 > 1 million individuals will be affected annually. High-throughput sequencing technologies led to the identification of several molecular HCC subclasses that can be broadly grouped into 2 major subgroups, each characterized by specific morphological and phenotypical features. It is likely that this increasing knowledge and a more appropriate characterization of HCC at the pathological level will impact HCC patient management.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Prognosis
PubMed: 34294938
DOI: 10.32074/1591-951X-295 -
Chinese Medical Journal May 2023Hepatocellular carcinoma (HCC) is the most common type of primary hepatocellular carcinoma (PHC). Early diagnosis of HCC remains the key to improve the prognosis. In... (Review)
Review
Hepatocellular carcinoma (HCC) is the most common type of primary hepatocellular carcinoma (PHC). Early diagnosis of HCC remains the key to improve the prognosis. In recent years, with the promotion of the concept of precision medicine and more in-depth analysis of the biological mechanism underlying HCC, new diagnostic methods, including emerging serum markers, liquid biopsies, molecular diagnosis, and advances in imaging (novel contrast agents and radiomics), have emerged one after another. Herein, we reviewed and analyzed scientific advances in the early diagnosis of HCC and discussed their application and shortcomings. This review aimed to provide a reference for scientific research and clinical practice of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Early Diagnosis; Precision Medicine
PubMed: 36939276
DOI: 10.1097/CM9.0000000000002641 -
Future Oncology (London, England) Apr 2021For a decade, sorafenib remained the only approved first-line treatment and standard of care for advanced hepatocellular carcinoma. The treatment landscape has been... (Review)
Review
For a decade, sorafenib remained the only approved first-line treatment and standard of care for advanced hepatocellular carcinoma. The treatment landscape has been evolving rapidly over the past 2 years with the approval of additional first-and second-line systemic treatments, most of which are targeted therapies. The expected approval of immunotherapies constitutes a paradigm shift: for the first time in years, a checkpoint inhibitor in combination with a VEGF antibody recently outperformed sorafenib with regards to efficacy. The wider availability of systemic therapies increases the chance for longer overall survival but raises new questions concerning the role of local options, treatment choice and sequential treatment. Following an expert discussion at the German Cancer Congress 2020 in Berlin, this article aims to summarize the current evidence on and experience of treatment choice and sequence in first- and second-line therapy.
Topics: Carcinoma, Hepatocellular; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Liver Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Treatment Outcome
PubMed: 33307782
DOI: 10.2217/fon-2020-0758 -
British Journal of Cancer Jan 2023Hepatocellular carcinoma is the most prevalent form of primary liver cancer with a multifactorial aetiology comprising genetic, environmental, and behavioural factors.... (Review)
Review
Hepatocellular carcinoma is the most prevalent form of primary liver cancer with a multifactorial aetiology comprising genetic, environmental, and behavioural factors. Evading cell death is a defining hallmark of hepatocellular carcinoma, underpinning tumour growth, progression, and therapy resistance. Ferroptosis is a form of nonapoptotic cell death driven by an array of cellular events, including intracellular iron overload, free radical production, lipid peroxidation and activation of various cell death effectors, ultimately leading to rupture of the plasma membrane. Although induction of ferroptosis is an emerging strategy to suppress hepatocellular carcinoma, malignant cells manage to develop adaptive mechanisms, conferring resistance to ferroptosis and ferroptosis-inducing drugs. Herein, we aim at elucidating molecular mechanisms and signalling pathways involved in ferroptosis and offer our opinions on druggable targets and new therapeutic strategy in an attempt to restrain the growth and progression of hepatocellular carcinoma through induction of ferroptotic cell death.
Topics: Humans; Carcinoma, Hepatocellular; Ferroptosis; Iron; Liver Neoplasms; Cell Death
PubMed: 36229582
DOI: 10.1038/s41416-022-01998-x -
Journal of Hepatology Jun 2022Hepatocellular carcinoma (HCC) currently represents the fifth most common malignancy and the third-leading cause of cancer-related death worldwide, with incidence and... (Review)
Review
Hepatocellular carcinoma (HCC) currently represents the fifth most common malignancy and the third-leading cause of cancer-related death worldwide, with incidence and mortality rates that are increasing. Recently, artificial intelligence (AI) has emerged as a unique opportunity to improve the full spectrum of HCC clinical care, by improving HCC risk prediction, diagnosis, and prognostication. AI approaches include computational search algorithms, machine learning (ML) and deep learning (DL) models. ML consists of a computer running repeated iterations of models, in order to progressively improve performance of a specific task, such as classifying an outcome. DL models are a subtype of ML, based on neural network structures that are inspired by the neuroanatomy of the human brain. A growing body of recent data now apply DL models to diverse data sources - including electronic health record data, imaging modalities, histopathology and molecular biomarkers - to improve the accuracy of HCC risk prediction, detection and prediction of treatment response. Despite the promise of these early results, future research is still needed to standardise AI data, and to improve both the generalisability and interpretability of results. If such challenges can be overcome, AI has the potential to profoundly change the way in which care is provided to patients with or at risk of HCC.
Topics: Algorithms; Artificial Intelligence; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Machine Learning
PubMed: 35589255
DOI: 10.1016/j.jhep.2022.01.014