Hepatocellular Carcinoma in Non-cirrhotic Liver Arises with a More Advanced Tumoral Appearance: A Single-Center Cohort Study

Demirtaş, Coşkun Özer; Tolu, Tugba; Keklikkıran, Çağlayan; Özdoğan, Osman; Gündüz, Feyza

doi:10.5152/tjg.2021.20677

Cited by 4 publications

(8 citation statements)

References 31 publications

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“…Previous studies examining multiple predictors of survival in HCC-NCL have reported controversial results. Nonetheless, this study identified larger tumors as a risk factor for survival in HCC-NCL, consistent with several other studies (Q-song et al 2021 ; Yip et al 2013 ; Wörns et al 2012 ; Dasari et al 2020 ; Penzkofer et al 2022 ; Demirtas et al 2021 ; Arnaoutakis et al 2013 ). As tumor prognosis gains more attention, more and more tumors at substantial sites are incorporating mass size into AJCC staging.…”

Section: Discussionsupporting

confidence: 91%

“…Larger tumors also decrease the likelihood that a patient will undergo radical surgery. Nevertheless, previous retrospective studies have not consistently identified larger tumors as a risk factor impacting survival in patients with HCC-NCL (Demirtas et al 2021 ; Verhoef et al 2004 ; Schütte et al 2014 ; Xu et al 2008 ). These discrepancies may be related to variances in patient characteristics and differences in sample sizes.…”

Section: Discussionmentioning

confidence: 98%

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SEER-based risk stratification system for patients with primary non-cirrhotic liver cancer

Cao

Jiang

et al. 2023

J Cancer Res Clin Oncol

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Background Little research has been done on the factors affecting the survival of patients with non-cirrhotic hepatocellular carcinoma (HCC-NCL). Our aim was to develop and validate a nomogram and a new risk stratification system that can evaluate overall survival (OS) in HCC-NCL patients. Methods We retrospectively analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2019 to study HCC-NCL patients. The patients were randomly split into training and validation groups at a 7:3 ratio and subjected to single-factor and multi-factor COX regression analysis. We then developed a nomogram and evaluated its accuracy and clinical validity using time-dependent ROC, DCA, and calibration curves. We compared the nomogram with the AJCC staging system by calculating C-index, NRI, and IDI. Finally, we used Kaplan–Meier curves to compare the nomogram and AJCC staging. These analyses were performed without altering the original intended meaning. Results AFP levels, surgical intervention, T-stage, tumor size, and M-stage were independent prognostic indicators for overall survival among the HCC-NCL population studied. We developed a nomogram based on these factors, and time-dependent ROC, calibration curves, DCA analyses, and C-index proved its accuracy. Compared to the AJCC staging system, the nomogram showed better prognostic accuracy through time-dependent ROC, DCA analyses, C-index, NRI, IDI, and Kaplan–Meier curves. Conclusion We have developed and validated a survival nomogram applicable to HCC-NCL patients, with risk stratification. Our nomogram offers personalized treatment and management options superior to those provided by the AJCC staging system.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 98%

SEER-based risk stratification system for patients with primary non-cirrhotic liver cancer

Cao

Jiang

et al. 2023

J Cancer Res Clin Oncol

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“…Survival outcomes in the univariate analysis of non-cirrhotic HCC were comparable to those of HCCs arising in a cirrhotic liver, consistent with prior research findings 12 , 20 , 30 , 31 . The non-cirrhotic cryptogenic group presented with the worst survival as compared to other groups given they were detected generally late and with advanced and symptomatic disease.…”

Section: Discussionsupporting

confidence: 86%

“…Previous studies have reported indeterminate causes in up to 48% of non-cirrhotic HCC cases, raising concerns about potential misclassification due to incomplete data hindering definitive determinations 5 , 11 , 13 – 15 , 18 , 19 . Among the studies on cryptogenic causes of HCC, a South Korean investigation reported the lowest rate (< 8%) of cryptogenic HCC (cirrhotic and non-cirrhotic), while Dutch, United States, and Turkish studies documented frequencies ranging between 11 and 19% 12 , 13 , 20 , 21 . Our study firmly establishes cryptogenic etiology as the dominant underlying liver condition in non-cirrhotic HCC patients within our cohort.…”

Section: Discussionmentioning

confidence: 99%

Cryptogenic non-cirrhotic HCC: Clinical, prognostic and immunologic aspects of an emerging HCC etiology

Beudeker,

Guha,

Stoyanova

et al. 2024

Sci Rep

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The incidence of hepatocellular carcinoma (HCC) in non-cirrhotic livers is rising significantly, but clear risk factors for screening remain elusive. This study sought to characterize non-cirrhotic HCC etiologies. HCC cases from 2009 to 2020 in a Dutch referral center were examined, revealing 371 out of 1654 cases (22%) as non-cirrhotic. Notably, the incidence of non-cirrhotic HCC increased by 61% in the time frame between 2009 and 2020. Interestingly 39% of non-cirrhotic HCC cases had cryptogenic origins. Cryptogenic non-cirrhotic HCC exhibited similarities with non-cirrhotic NAFLD HCC, but displayed advanced tumor stages, lower surgical rates, and a more frequent presence of symptoms, which substantiated in poor survival rates. Advanced cryptogenic non-cirrhotic HCC stages exhibited elevated serum interleukin-6 levels compared to non-cirrhotic HCC with defined etiologies. Comparative analysis encompassing cryptogenic and NAFLD non-cirrhotic HCC cohorts and controls unveiled comparable circulating immune biomarker profiles and PNPLA3 polymorphisms. To conclude, the primary etiology of non-cirrhotic HCC in our cohort has not defined risk factors. This cryptogenic variant exhibits distinct traits, such as advanced tumors and increased symptoms, and most resemble burned-out NAFLD. Understanding this HCC variant is crucial for improving screening and management strategies.

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“…Patients with NAFLD and HCC without cirrhosis have larger tumors, but more often, they have well-differentiated tumors and a single nodule compared to those with cirrhosis[ 59 , 69 , 70 ]. On the other hand, due to late diagnosis, some cases have a higher rate of vascular invasion and extra-hepatic metastasis[ 71 ]. Frequently, the nontumor liver has significant steatosis and histological findings of steatohepatitis[ 72 ] (Figure 1 ).…”

Section: Histopathological Aspects Of Nafld-related Hccmentioning

confidence: 99%

Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis

Tovo¹,

Mattos²,

Coral³

et al. 2023

World J Gastroenterol

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Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.

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Hepatocellular Carcinoma in Non-cirrhotic Liver Arises with a More Advanced Tumoral Appearance: A Single-Center Cohort Study

Cited by 4 publications

References 31 publications

SEER-based risk stratification system for patients with primary non-cirrhotic liver cancer

SEER-based risk stratification system for patients with primary non-cirrhotic liver cancer

Cryptogenic non-cirrhotic HCC: Clinical, prognostic and immunologic aspects of an emerging HCC etiology

Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis

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