New concepts in the treatment of hepatocellular carcinoma

Sidali, Sabrina; Trépo, Eric; Nault, Jean–Charles

doi:10.1002/ueg2.12286

Cited by 50 publications

(41 citation statements)

References 87 publications

(152 reference statements)

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“…The incidence of hepatocellular carcinoma (HCC), the third most prevalent cancer-related cause of death worldwide, is rising ( 38 ). Infection with the hepatitis C and B viruses ( 39 ), alpha-1-antitrypsin deficiency ( 40 ), heavy alcoholism ( 41 ) cirrhosis ( 42 ), hemochromatosis ( 43 ), are risk factors associated with HCC.…”

Section: Discussionmentioning

confidence: 99%

miRNome of Child A hepatocellular carcinoma in Egyptian patients

et al. 2023

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IntroductionHepatocellular carcinoma (HCC) has different etiologies that contribute to its heterogeneity. In regards to the number of HCC patients, Egypt ranks third in Africa and fifteenth worldwide. Despite significant advancements in HCC diagnosis and treatment, the precise biology of the tumor is still not fully understood, which has a negative impact on patient outcomes.MethodsAdvances in next-generation sequencing (NGS) have increased our knowledge of the molecular complexity of HCC.Results & discussionIn this research, 16 HCC and 6 tumor adjacent tissues (control) of Child A Egyptian patients were successfully profiled for the expression profile of miRNAs by NGS. Forty-one differentially expressed miRNAs (DEMs) were found by differential expression analysis, with 31 being upregulated and 10 being downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then conducted on these differentially expressed miRNAs revealing that Sensitivity and specificity analysis showed that hsa-miR-4488, hsa-miR-3178, and hsa-miR-3182 were unique miRNAs as they are expressed in HCC tissues only. These miRNAs were all highly involved in AMPK signaling pathways. However, hsa-miR-214-3p was expressed in control tissues about eight times higher than in cancer tissues and was most abundant in “pathways in cancer and PI3K-Akt signaling pathway” KEGG terms. As promising HCC diagnostic markers, we here suggest hsa-miR-4488, hsa-miR-3178, hsa-miR-3182, and hsa-miR-214-3p. We further urge future research to confirm these markers' diagnostic and prognostic potential as well as their roles in the pathophysiology of HCC.

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Section: Discussionmentioning

confidence: 99%

miRNome of Child A hepatocellular carcinoma in Egyptian patients

et al. 2023

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“…This system combines liver biochemical parameters, radiological imaging and performance status with treatment guidelines [Child-Pugh, Model for End-Stage Liver Disease (MELD), Albumin-Bilirubin (ALBI) score, Eastern Cooperative Oncology Group (ECOG) Performance Scale] [ 14 , 15 ]. The algorithm has recently undergone an update, introducing the concept of treatment stage migration (TSM) [ 16 ]. TSM requires valuable input from the multidisciplinary team (MDT) as it seeks to consider non-hepatic factors, such as age, donor availability, and co-morbidities, in order to ‘assign’ patients to a more advanced treatment stage than initially recommended by BCLC staging guidelines [ 4 ].…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

The Role of Ablative Techniques in the Management of Hepatocellular Carcinoma: Indications and Outcomes

et al. 2023

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The management of hepatocellular carcinoma (HCC) remains complex and will continue to rely on the multidisciplinary input of hepatologists, surgeons, radiologists, oncologists and radiotherapists. With the appropriate staging of patients and selection of suitable treatments, the outcomes for HCC are improving. Surgical treatments encompassing both liver resection and orthotopic liver transplantation (OLT) are the definitive curative-intent options. However, patient suitability, as well as organ availability, pose essential limitations. Consequently, non-surgical options, such as ablative techniques, play an increasingly important role, especially in small HCCs, where overall and disease-free survival can be comparable to surgical resection. Ablative techniques are globally recommended in recognised classification systems, showing increasingly promising results. Recent technical refinements, as well as the emerging use of robotic assistance, may expand the treatment paradigm to achieve improved oncological results. At present, in very early stage and early stage unresectable disease, percutaneous thermal ablation is considered the treatment of choice. Owing to their different features, various ablative techniques, including radiofrequency ablation, microwave ablation, cryotherapy ablation and irreversible electroporation, have been shown to confer different comparative advantages and applicability. We herein review the role of available ablative techniques in the current complex multidisciplinary management of HCC, with a main focus on the indications and outcomes, and discuss future perspectives.

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“…IO combination therapy has been introduced and practice changing in first-line therapy of HCC in BCLC stage C. The combination of atezolizumab (PD-L1-inhibitor) and bevacizumab (VEGF-inhibitor) showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma [ 238 ]. Based on the results of the IMbrave-150 trial the combination of bevacizumab and atezolizumab became a new standard of care in first-line treatment of HCC in BCLC stage C [ 13 , 14 ]. In this randomized phase III clinical trial, the combination of atezolizumab and bevacizumab has demonstrated superiority compared to sorafenib.…”

Section: Systemic Therapy For Hcc Bclc Cmentioning

confidence: 99%

“…Updated classifications and treatment options are illustrated as red boxes and arrows. This updated BCLC system further contains new workflows during radiological progression within between the stages (BCLCp-B, BCLCp-C1, BCLCp-C2) [ 13 , 14 ].…”

Section: Figurementioning

confidence: 99%

Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

et al. 2022

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

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New concepts in the treatment of hepatocellular carcinoma

Cited by 50 publications

References 87 publications

miRNome of Child A hepatocellular carcinoma in Egyptian patients

miRNome of Child A hepatocellular carcinoma in Egyptian patients

The Role of Ablative Techniques in the Management of Hepatocellular Carcinoma: Indications and Outcomes

Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

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