Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B

Papatheodoridis, George; Sypsa, Vana; Dalekos, George Ν.; Yurdaydın, Cihan; Boemmel, Florian van; Buti, María; Calleja, José Luís; Chi, Heng; Goulis, John; Manolakopoulos, Spilios; Loglio, Alessandro; Voulgaris, Theodoros; Gatselis, Nikolaos; Keskın, Onur; Veelken, Rhea; López-Gómez, Marta; Hansen, Bettina E.; Savvidou, Savvoula; Κourikou, Αnastasia; Vlachogiannakos, John; Galanis, Kostas; İdilman, Ramazan; Esteban, Rafael; Janssen, Harry L.A.; Berg, Thomas; Lampertico, Pietro

doi:10.1016/j.jhep.2020.01.007

Cited by 90 publications

(118 citation statements)

References 25 publications

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“…The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used algorithm for determining the course of treatment of HCC [ 4 ]. Although antiviral therapy contributed to improve prediction of HCC risk [ 5 ] patients are often diagnosed at an advanced stage [ 6 ]. Molecular-targeted agents (MTAs) are recommended for the treatment of patients with intermediate or advanced stage HCC [ 7 , 8 ] and have increasingly been used as the standard therapy for this patient population.…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Adverse Events for Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Retrospective Study

Shimose

Iwamoto

Nishizaki

et al. 2020

Cancers

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We sought to investigate the clinical profile(s) associated with the discontinuation of lenvatinib (LEN) due to severe adverse events (DLSAE) in patients with unresectable hepatocellular carcinoma (HCC). This retrospective study enrolled 177 patients with HCC treated with LEN. Independent factors associated with DLSAE were advanced age, albumin-bilirubin (ALBI) grade 2, fatigue grade ≥ 3, and appetite loss ≥ 2. The overall survival (OS) in the group that did not require DLSAE was significantly longer compared to the group that did require DLSAE (median survival time (MST): not reached vs. 12.8 months, p < 0.001). Moreover, advanced age was the most important variable for DLSAE in a decision tree analysis. Hypertension and hand-foot-skin-reaction (HFSR) were also significantly associated with longer survival, and the occurrence of hypertension was the earliest predictor for improved prognosis, while appetite loss and development of grade ≥ 3 fatigue were predictive of a poor prognosis. We concluded that the appearance of hypertension has potential as an early surrogate marker to predict improved prognosis. Moreover, careful management to avoid discontinuation of treatment leads to longer survival in patients receiving LEN.

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Section: Introductionmentioning

confidence: 99%

Clinical Significance of Adverse Events for Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Retrospective Study

Shimose

Iwamoto

Nishizaki

et al. 2020

Cancers

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“…Malignant primary liver tumors are the second leading cause of cancer-related death worldwide, with an increasing incidence in almost all countries [1]. Hepatocellular carcinoma (HCC) is about 85-90% of primary liver cancer and its main risk factors are hepatitis B (HBV) or C (HCV) infection, alcohol consumption and metabolic syndrome [2,3]. Early HCC can be treated by local ablation, surgical resection or liver transplantation.…”

Section: Introductionmentioning

confidence: 99%

Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma

Liu

Zhang

Chao

et al. 2020

Cancer Immunol Immunother

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The "macrotrabecular-massive" (MTM) pattern of hepatocellular carcinoma (HCC) has been suggested to represent a distinct HCC subtype and is associated with specific molecular features. Since the immune microenvironment is heterogenous in HCC, it is important to evaluate the immune microenvironment of this novel variant. CMTM6, a key regulator of PD-L1, is an important immunocheckpoint inhibitor. This study aimed to evaluate the prognostic effect of CMTM6/PD-L1 coexpression and its relationship with inflammatory cells in HCC. We analyzed 619 HCC patients and tumors were classified into MTM and non-MTM HCC subtypes. The expression levels of CMTM6 and PD-L1 in tumor and inflammatory cells were evaluated by immunohistochemistry. The density of inflammatory cells in the cancer cell nest was calculated. Tumoral PD-L1 expression and inflammatory cell density were higher in the MTM type than in the non-MTM type. CMTM6-high expression was significantly associated with shorter OS and DFS than CMTM6-low expression in the whole HCC patient population and the MTM HCC patient population. Moreover, MTM HCC patients with CMTM6/PD-L1 coexpression experienced a higher risk of HCC progression and death. In addition, CMTM6/PD-L1 coexpression was shown to be related to a high density of inflammatory cells. Notably, a new immune classification, based on CMTM6/PD-L1 coexpression and inflammatory cells, successfully stratified OS and DFS in MTM HCC. CMTM6/PD-L1 coexpression has an adverse effect on the prognosis of HCC patients, especially MTM HCC patients. Our study provides evidence for the combination of immune status assessment with anti-CMTM6 and anti-PD-L1 therapy in MTM HCC patients.

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“…Therefore, undetectable HBV DNA may be used as a factor constituting a predictive model for HCC development. Furthermore, previous reports showed that HBsAg, [20][21][22] HBcrAg, [21][22][23] HBV DNA level, 19,24 liver stiffness 25 and M2BPGi [26][27][28][29][30] during treatment were useful for stratification of carcinogenic risk. Future studies are required to determine whether a more accurate carcinogenic risk prediction model could be constructed by combining these scores with PAGE-B.…”

Section: Predictability Of Risk Models For Hcc Developmentmentioning

confidence: 99%

Dynamic evaluation of hepatocellular carcinoma prediction models in patients with chronic hepatitis B receiving nucleotide/nucleoside analogue treatment

Kirino

Tamaki

Kurosaki

et al. 2021

Journal of Viral Hepatitis

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Carcinogenesis risk scores for chronic hepatitis B have been proposed, but it remains unclear whether these scores during nucleoside/nucleotide analogue (NA) therapy are useful for risk assessment. In this study, we examined changes of these scores and the predictability during NA treatment. 432 patients with no history of hepatocellular carcinoma (HCC) treated with NA were enrolled. PAGE-B, modified PAGE-B (mPAGE-B), and REACH-B scores were calculated at NA administration, 1 and 2 years after administration. The median follow-up duration was 5.1 years, during which 37 patients (8.6%) developed HCC. Cumulative incidence HCC development in patients with high risk of PAGE at NA administration, and 1 and 2 years after NA administration was significantly higher than those with intermediate and low-risk groups (p < .05 for all time points), whereas HCC incidence in patients with high risk of mPAGE-B and REACH-B at 2 years after NA administration were equivalent to those with intermediate and low-risk groups (p = .2 for mPAGE-B, and p = .1 for REACH-B). The area under the receiver operating characteristic (AUROC)

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Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B

Cited by 90 publications

References 25 publications

Clinical Significance of Adverse Events for Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Retrospective Study

Clinical Significance of Adverse Events for Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Retrospective Study

Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma

Dynamic evaluation of hepatocellular carcinoma prediction models in patients with chronic hepatitis B receiving nucleotide/nucleoside analogue treatment

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