A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis

Fujiwara, Naoto; Kobayashi, Masahiro; Fobar, Austin J.; Hoshida, Ayaka; Marquez, Cesia Ammi; Koneru, Bhuvaneswari; Panda, Gautam; Taguri, Masataka; Qian, Tongqi; Raman, Indu; Li, Quan-Zhen; Hoshida, Hiroki; Sezaki, Hitomi; Kumada, Hiromitsu; Tateishi, Ryosuke; Yokoo, Takeshi; Yopp, Adam C.; Chung, Raymond T.; Fuchs, Bryan C.; Baumert, Thomas F.; Marrero, Jorge A.; Parikh, Neehar D.; Zhu, Shijia; Singal, Amit G.; Hoshida, Yujin

doi:10.1016/j.medj.2021.03.017

Cited by 43 publications

(34 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This proportion may be even higher in patients with nonalcohol-related fatty liver disease, in whom HCC is prone to develop in the absence of cirrhosis . These studies highlight the need for better identification algorithms and diagnostic pathways for patients with advanced fibrosis or cirrhosis who are at risk for HCC, as well as development of risk stratification biomarkers . Population-based screening using existing noninvasive fibrosis markers has yet to be shown to be feasible, and ongoing efforts to improve cirrhosis detection are needed.…”

Section: Discussionmentioning

confidence: 99%

Barriers to Surveillance for Hepatocellular Carcinoma in a Multicenter Cohort

et al. 2022

Self Cite

View full text Add to dashboard Cite

IMPORTANCEHepatocellular carcinoma (HCC) surveillance is underused in clinical practice, which may be owing to patient and clinician barriers. OBJECTIVE To characterize HCC surveillance barriers and associations with clinical outcomes in a multicenter cohort of patients with cirrhosis. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included 5 medical centers in the United States. Patients with cirrhosis and newly diagnosed HCC treated from 2014 to 2018 were included. Data were analyzed from June 2021 to February 2022. EXPOSURE Surveillance completion in the 36-month period prior to HCC diagnosis. MAIN OUTCOMES AND MEASURES Surveillance receipt was classified as semiannual, annual, or no surveillance. Multivariable logistic regression analysis was used to identify factors associated with semiannual surveillance. We conducted multivariable logistic and Cox regression analyses to characterize associations between surveillance completion with curative treatment and overall survival. RESULTS A total 629 eligible patients (median [IQR] age, 63.6 [56.2-71.0] years; 491 [78.1%] men) were assessed, including 7 American Indian or Alaska Native patients (1.1%), 14 Asian patients (2.2), 176 Black patients (28.0%), 86 Hispanic patients (13.1%), and 340 White patients (54.1%). Nearly two-thirds of the cohort had no surveillance prior to HCC diagnosis (mean [range by site] 63.7%[37.9%-80.4%]), with a mean (range by site) of 14.0% (5.3%-33.3%) of patients having received semiannual surveillance and 22.3% (14.3%-28.8%) of patients having received annual surveillance.The most common reasons for no surveillance were lack of surveillance orders or nonadherence (mean [range by site], 82.4% [66.7%-92.4%], although a mean (range by site) of 17.6% (10.2%-22.1%) of patients had unrecognized cirrhosis at HCC presentation. Semiannual surveillance was associated with hepatitis B infection (odds ratio [OR], 3.06 [95% CI, 1.24-7.23]) and inversely associated with Black race (OR, 0.41 [95% CI, 0.20-0.80]) and lack of cirrhosis recognition (OR, 0.14 [95% CI, 0.02-0.46]). Semiannual HCC surveillance was significantly associated with curative treatment receipt (OR, 2.73 [95% CI, 1.60-4.70]) but not overall survival (HR, 0.81 [95% CI, 0.55-1.18]). CONCLUSIONS AND RELEVANCEIn this cohort study of patients with cirrhosis, HCC surveillance was underused in more than 80% of patients and associated with failures across the screening process. Dedicated programs to improve cirrhosis detection and HCC surveillance attainment are needed.

show abstract

Section: Discussionmentioning

confidence: 99%

Barriers to Surveillance for Hepatocellular Carcinoma in a Multicenter Cohort

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…An in-depth discussion of HCC risk stratification in patients with NAFLD is beyond the scope of this review. However, in brief, several risk models incorporating clinical risk factors, genetic factors, and molecular factors have been proposed, with most not yet having been sufficiently validated for routine use in clinical practice [ 42 - 45 ]. If sufficiently validated, these risk models may facilitate a more individualized precision screening approach to targeted HCC surveillance to those at the highest risk [ 46 , 47 ].…”

Section: Identification Of the At-risk Nafld Populationmentioning

confidence: 99%

Hepatocellular carcinoma surveillance in patients with non-alcoholic fatty liver disease

2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…A relatively large phase III RCT is recruiting participants to assess simvastatin in compensated cirrhosis for HCC development as a part of composite secondary end point (SACRED trial; NCT03654053). Atorvastatin is being evaluated in another phase II RCT using modulation of an HCC risk biomarker, prognostic liver secretome signature, 38 47 as the primary end point (NCT05028829). A nationwide multicenter clinical trial of lipophilic statin is being launched to assess lipophilic statin on adverse outcomes in cirrhotics with support from the NIH/NIDDK Liver Cirrhosis Network.…”

Section: Potential Hcc Chemoprevention Therapies With Generic Agentsmentioning

confidence: 99%

Hepatocellular Carcinoma Chemoprevention with Generic Agents

et al. 2022

Self Cite

View full text Add to dashboard Cite

Liver cancer, mainly hepatocellular carcinoma (HCC), remains a major cause of cancer-related death worldwide. With the global epidemic of obesity, the major HCC etiologies have been dynamically shifting from viral to metabolic liver diseases. This change has made HCC prevention difficult with increasingly elusive at-risk populations as rational target for preventive interventions. Besides ongoing efforts to reduce obesity and metabolic disorders, chemoprevention in patients who already have metabolic liver diseases will have a significant impact on the poor HCC prognosis. Hepatitis B- and C-related HCC incidences have been substantially reduced by the new anti-virals, but HCC risk can persist over a decade even after successful viral treatment, highlighting the need for HCC-preventive measures also in these patients. Experimental and retrospective studies have suggested potential utility of generic agents such as lipophilic statins and aspirin for HCC chemoprevention given their well characterized safety profile, although anticipated efficacy may be modest. In this review, we overview recent clinical and translational studies of generic agents in the context of HCC chemoprevention under the contemporary HCC etiologies. We also discuss newly emerging approaches to overcome the challenges in clinical testing of the agents to facilitate their clinical translation.

show abstract

A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis

Cited by 43 publications

References 87 publications

Barriers to Surveillance for Hepatocellular Carcinoma in a Multicenter Cohort

Barriers to Surveillance for Hepatocellular Carcinoma in a Multicenter Cohort

Hepatocellular carcinoma surveillance in patients with non-alcoholic fatty liver disease

Hepatocellular Carcinoma Chemoprevention with Generic Agents

Contact Info

Product

Resources

About