Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

Biomedicines, Journal Year: 2022, Volume and Issue: 10(12), P. 3202 - 3202

Published: Dec. 9, 2022

Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation progression are favored by different etiological risk factors including hepatitis B virus (HBV) C (HCV) infection, non-/and alcoholic fatty disease (N/AFLD), tobacco smoking. In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute development HCC. The multitude complexity pathomechanisms also reflect difficulties tailored medical therapy Treatment options strictly dependent on tumor staging function, which structured updated Barcelona Clinic Liver Cancer classification system. Surgical resection, local ablative techniques, transplantation valid curative therapeutic early stages. For multifocal metastatic diseases, systemic recommended. While Sorafenib had been standalone first-line decades, recent developments led approval new treatment as well second-line treatment. Anti-PD-L1 directed combination therapies either anti-VEGF agents or anti-CTLA-4 active substances have implemented standard setting. However, data from clinical trials indicate responses specific regimens depending underlying pathogenesis hepatocellular cancer. Therefore, histopathological examinations re-emphasized current international guidelines addition standardized radiological diagnosis using contrast-enhanced cross-sectional imaging. this review, we emphasize knowledge carcinoma. On occasion, sequences advanced stages according recently system algorithm (first-, second-, third-line treatment) summarized. Furthermore, discuss novel precautional pre-therapeutic approaches vaccination, adoptive cell transfer, locoregional enhancement, non-coding RNA-based promising options. These treatments may prolong overall regard quality life function mainstay therapy.

Language: Английский

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Role of immune responses in the development of NAFLD-associated liver cancer and prospects for therapeutic modulation

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(2), P. 538 - 551

Published: March 7, 2023

The liver is the central metabolic organ of body, regulating energy and lipid metabolism, while also having potent immunological functions. Overwhelming capacity via obesity a sedentary lifestyle leads to hepatic accumulation, chronic necro-inflammation, enhanced mitochondrial/endoplasmic reticulum stress development non-alcoholic fatty disease (NAFLD), its more severe form steatohepatitis (NASH). Based on an improved understanding pathophysiological mechanisms, specifically targeting pathways prevent or slow down progression NAFLD cancer will become possible. Genetic/environmental factors are known contribute NASH cancer. complex pathophysiology NAFLD-NASH reflected by environmental factors, particularly gut microbiome products. NAFLD-associated HCC most often occurs in context chronically inflamed cirrhotic liver. Recognition alarmins metabolites derived from microbiota metabolically injured create strong inflammatory milieu supported innate adaptive immunity. Several recent studies indicate that steatosis induces auto-aggressive CD8+CXCR6+PD1+ T cells eliminate parenchymal non-parenchymal antigen-independent manner. This promotes damage pro-tumorigenic environment. possess exhausted, hyperactivated, resident phenotype; they trigger transition might be responsible for weaker responses immune checkpoint inhibitors - particular atezolizumab/bevacizumab. Here, we provide overview NASH-related inflammation/pathogenesis, focusing new discoveries role cells. review discusses preventive measures halt therapeutic strategies manage patients with NASH-HCC.

Language: Английский

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Immune checkpoint inhibitors in hepatocellular carcinoma: emerging challenges in clinical practice

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2023, Volume and Issue: 8(8), P. 760 - 770

Published: June 16, 2023

Language: Английский

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The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease

Hepatology International, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

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Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies

Cancers, Journal Year: 2022, Volume and Issue: 15(1), P. 23 - 23

Published: Dec. 20, 2022

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and sixth frequent in world, being third cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH) characterized by fatty infiltration, oxidative stress necroinflammation liver, with or without fibrosis, which can progress to advanced cirrhosis HCC. Obesity, metabolic syndrome, insulin resistance, diabetes exacerbates course NASH, elevate risk The growing prevalence obesity are related increasing incidence may play a role HCC epidemiology worldwide. In addition, initiation progression driven reprogramming metabolism, indicates appreciation metabolism pathogenesis this disease. Although no specific preventive pharmacological treatments have recommended for dietary restriction exercise recommended. This review focuses on molecular connections between including genetic factors, highlighting aberrant epigenetic alterations development NASH. Current therapeutic aspects NASH/HCC also reviewed.

Language: Английский

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MAFLD: an optimal framework for understanding liver cancer phenotypes

Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 58(10), P. 947 - 964

Published: July 20, 2023

Hepatocellular carcinoma has a substantial global mortality burden which is rising despite advancements in tackling the traditional viral risk factors. Metabolic (dysfunction) associated fatty liver disease (MAFLD) most prevalent disease, increasing parallel with epidemics of obesity, diabetes and systemic metabolic dysregulation. MAFLD major factor behind this sustained rise HCC incidence, both as single entity often via synergistic interactions other diseases. Mechanisms MAFLD-related are complex but crucially underpinned by dysregulation variable contributions from interacting modifiers related to environment, genetics, dysbiosis immune distinct clinical presentation, notably its common occurrence non-cirrhotic disease. This just one several challenges effective surveillance programmes. The response immune-checkpoint therapy currently controversial, further complicated high prevalence individuals aetiologies. In review, we highlight current data on epidemiology, characteristics, outcomes screening controversies. addition, concepts that have arisen because paradigm such MAFLD/NAFLD non-overlapping groups, dual aetiology tumours sub-phenotypes reviewed.

Language: Английский

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Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients

Journal of Cancer Research and Clinical Oncology, Journal Year: 2023, Volume and Issue: 149(10), P. 7565 - 7577

Published: March 28, 2023

Language: Английский

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Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma: A systematic review and meta-analysis

Clinical and Molecular Hepatology, Journal Year: 2024, Volume and Issue: 30(3), P. 436 - 448

Published: April 16, 2024

Background/Aims: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. MAFLD diagnostic criteria allows objective diagnosis in the presence steatosis plus defined markers dysfunction, irrespective concurrent disease. We aimed determine total prevalence HCC cohorts (total-MAFLD), including with as their sole (single-MAFLD), and those where was a contributary factor (mixed-MAFLD).Methods: This systematic review meta-analysis included studies systematically ascertaining cohorts, using international expert panel ethnicity-specific BMI cut-offs. A comparison clinical tumour characteristics performed between single-MAFLD, mixed-MAFLD, non-MAFLD HCC.Results: 22 (56,565 individuals HCC) were included. Total single-MAFLD 48.7% (95% confidence interval [CI] 34.5–63.0%) 12.4% CI 8.3–17.3%), respectively. In due chronic hepatitis B, C, alcohol-related disease, mixed-MAFLD 40.0% 30.2–50.3%), 54.1% 40.4–67.6%) 64.3% 52.7–75.0%), Mixed-MAFLD had significantly higher likelihood cirrhosis lower metastatic spread compared HCC, platelet count macrovascular invasion HCC.Conclusions: common aetiology, but more so co-factor mixed-aetiology supporting use positive criteria.

Language: Английский

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Alcohol-associated liver cancer

Hepatology, Journal Year: 2024, Volume and Issue: 80(6), P. 1462 - 1479

Published: April 12, 2024

Heavy alcohol intake induces a wide spectrum of liver diseases ranging from steatosis, steatohepatitis, cirrhosis, and HCC. Although consumption is well-known risk factor for the development, morbidity, mortality HCC globally, alcohol-associated hepatocellular carcinoma (A-HCC) poorly characterized compared to viral hepatitis–associated Most A-HCCs develop after cirrhosis (AC), but direct carcinogenesis ethanol its metabolites A-HCC remains obscure. The differences between HCCs caused by other etiologies have not been well investigated in terms clinical prognosis, genetic or epigenetic landscape, molecular mechanisms, heterogeneity. Moreover, there huge gap basic research practice due lack preclinical models A-HCC. In current review, we discuss pathogenesis, heterogeneity, approaches, epigenetic, profiles A-HCC, insights into prospects future on potential effect cholangiocarcinoma metastasis also discussed.

Language: Английский

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Curcumin-Mediated Resistance to Lenvatinib via EGFR Signaling Pathway in Hepatocellular Carcinoma

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 612 - 612

Published: Feb. 14, 2023

Lenvatinib is a multi-kinase inhibitor approved as first-line treatment for patients with unresectable advanced hepatocellular carcinoma (HCC). However, its response rate unsatisfactory, primarily due to the acquisition of resistance, which limits clinical significance treating HCC. Recent evidence suggests that epidermal growth factor receptor (EGFR) activation can trigger Lenvatinib-resistance; and considered an important therapeutic target in Curcumin, one most studied naturally occurring botanicals robust anti-cancer activity, also reported be potent tyrosine kinase inhibitor. In this study, we hypothesized anti-EGFR potential Curcumin might help overcome resistance We established two Lenvatinib-resistant cells discovered combination exhibited synergistic anti-tumor efficacy resistant HCC cell lines. line previous reports, lines revealed significant EGFR, genomewide transcriptomic profiling analysis identified PI3K-AKT pathway was associated resistance. The dramatically suppressed gene protein expression EGFR-PI3K-AKT pathway, suggesting overcomes via inhibition EGFR. further validated these findings tumor spheroids derived from conclusion, we, first time, report reverses HCC, their has application adjunctive

Language: Английский

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