Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis

Background & Aims: Older adults have lower treatment eligibility and worse survival across cancer types; however, the association between age and outcomes in patients with hepatocellular carcinoma (HCC) has not been well characterized. Methods: We performed a search of the PubMed, Ovid MEDLI...

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Main Authors: Olgert Bardhi, Darine Daher, Mausam Patel, Karim Seif El-Dahan, Nicole E. Rich, Sukul Mitta, Neehar D. Parikh, Anjana Pillai, Laura M. Kulik, Ju Dong Yang, Anand V. Kulkarni, Purva Gopal, Amit G. Singal
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:JHEP Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S258955592500045X
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author Olgert Bardhi
Darine Daher
Mausam Patel
Karim Seif El-Dahan
Nicole E. Rich
Sukul Mitta
Neehar D. Parikh
Anjana Pillai
Laura M. Kulik
Ju Dong Yang
Anand V. Kulkarni
Purva Gopal
Amit G. Singal
author_facet Olgert Bardhi
Darine Daher
Mausam Patel
Karim Seif El-Dahan
Nicole E. Rich
Sukul Mitta
Neehar D. Parikh
Anjana Pillai
Laura M. Kulik
Ju Dong Yang
Anand V. Kulkarni
Purva Gopal
Amit G. Singal
author_sort Olgert Bardhi
collection DOAJ
description Background &amp; Aims: Older adults have lower treatment eligibility and worse survival across cancer types; however, the association between age and outcomes in patients with hepatocellular carcinoma (HCC) has not been well characterized. Methods: We performed a search of the PubMed, Ovid MEDLINE, and EMBASE databases from January 2000 to July 2022 to identify studies reporting tumor stage, curative treatment, and overall survival among patients with HCC, stratified by age. Using the DerSimonian and Laird method for a random-effects model, we calculated pooled risk ratios (RRs) for curative treatment receipt and hazard ratios (HRs) for overall survival among younger and older patients (per age thresholds in each study). Results: We identified 103 studies (n = 154,152 patients) that reported outcomes in younger vs. older patients with HCC. Younger patients were more likely to undergo curative treatment (RR 1.48, 95% CI 1.24–1.77; I2 = 99%), although few studies reported treatment among those with early-stage HCC. Younger patients had better survival than older patients (HR 0.87, 95% CI 0.83–0.92; I2 = 89%), which was consistent in subgroups using age thresholds of <70 years (HR 0.94, 95% CI 0.89–0.99; I2 = 78%) and <75 years (HR 0.83, 95% CI 0.70–0.98; I2 = 79%). Younger patients also had better survival in studies of patients with early-stage HCC (HR 0.78, 95% CI 0.65–0.94; I2 = 60%) and those undergoing curative therapy (HR 0.87, 95% CI 0.77–0.98; I2 = 87%). Conclusions: Older patients with HCC are less likely to receive curative treatment and have worse survival than their younger counterparts. Studies to identify factors associated with worse prognosis can inform intervention targets. Impact and implications: Older adults have worse survival across cancer types, although there are discordant data about the association between age and clinical outcomes in patients with hepatocellular carcinoma (HCC). Lower curative treatment receipt among older patients, despite similar early-stage presentation compared with younger patients, requires future studies to identify mediators that can inform intervention strategies that can increase curative treatment use. Worse survival observed among older patients appears to be primarily driven by non-liver-related mortality; however, few studies distinguish between liver and non-liver mortality. A better understanding of the prognostic value of comorbidity burden, in addition to age, can inform clinical decisions about stopping rules for HCC surveillance as well as the potential for HCC overdiagnosis and overtreatment.
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spelling doaj-art-08c21d31a213480c9f55a3b60fc4ebaf2025-08-20T03:25:05ZengElsevierJHEP Reports2589-55592025-06-017610136810.1016/j.jhepr.2025.101368Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysisOlgert Bardhi0Darine Daher1Mausam Patel2Karim Seif El-Dahan3Nicole E. Rich4Sukul Mitta5Neehar D. Parikh6Anjana Pillai7Laura M. Kulik8Ju Dong Yang9Anand V. Kulkarni10Purva Gopal11Amit G. Singal12Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USADepartment of Internal Medicine, University of Chicago, Chicago, IL, USADepartment of Internal Medicine, Northwestern University, Evanston, IL, USADepartment of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USADepartment of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, IndiaDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; Corresponding author. Address: Division of Digestive and Liver Diseases, University of Texas Southwestern, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas TX 75390-8887, USA. Tel.: +1 214 645 6029; fax: +1 214 645 6294.Background &amp; Aims: Older adults have lower treatment eligibility and worse survival across cancer types; however, the association between age and outcomes in patients with hepatocellular carcinoma (HCC) has not been well characterized. Methods: We performed a search of the PubMed, Ovid MEDLINE, and EMBASE databases from January 2000 to July 2022 to identify studies reporting tumor stage, curative treatment, and overall survival among patients with HCC, stratified by age. Using the DerSimonian and Laird method for a random-effects model, we calculated pooled risk ratios (RRs) for curative treatment receipt and hazard ratios (HRs) for overall survival among younger and older patients (per age thresholds in each study). Results: We identified 103 studies (n = 154,152 patients) that reported outcomes in younger vs. older patients with HCC. Younger patients were more likely to undergo curative treatment (RR 1.48, 95% CI 1.24–1.77; I2 = 99%), although few studies reported treatment among those with early-stage HCC. Younger patients had better survival than older patients (HR 0.87, 95% CI 0.83–0.92; I2 = 89%), which was consistent in subgroups using age thresholds of <70 years (HR 0.94, 95% CI 0.89–0.99; I2 = 78%) and <75 years (HR 0.83, 95% CI 0.70–0.98; I2 = 79%). Younger patients also had better survival in studies of patients with early-stage HCC (HR 0.78, 95% CI 0.65–0.94; I2 = 60%) and those undergoing curative therapy (HR 0.87, 95% CI 0.77–0.98; I2 = 87%). Conclusions: Older patients with HCC are less likely to receive curative treatment and have worse survival than their younger counterparts. Studies to identify factors associated with worse prognosis can inform intervention targets. Impact and implications: Older adults have worse survival across cancer types, although there are discordant data about the association between age and clinical outcomes in patients with hepatocellular carcinoma (HCC). Lower curative treatment receipt among older patients, despite similar early-stage presentation compared with younger patients, requires future studies to identify mediators that can inform intervention strategies that can increase curative treatment use. Worse survival observed among older patients appears to be primarily driven by non-liver-related mortality; however, few studies distinguish between liver and non-liver mortality. A better understanding of the prognostic value of comorbidity burden, in addition to age, can inform clinical decisions about stopping rules for HCC surveillance as well as the potential for HCC overdiagnosis and overtreatment.http://www.sciencedirect.com/science/article/pii/S258955592500045XLiver cancerElderlyDisparitiesPrognosisTreatment
spellingShingle Olgert Bardhi
Darine Daher
Mausam Patel
Karim Seif El-Dahan
Nicole E. Rich
Sukul Mitta
Neehar D. Parikh
Anjana Pillai
Laura M. Kulik
Ju Dong Yang
Anand V. Kulkarni
Purva Gopal
Amit G. Singal
Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis
JHEP Reports
Liver cancer
Elderly
Disparities
Prognosis
Treatment
title Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis
title_full Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis
title_fullStr Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis
title_full_unstemmed Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis
title_short Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis
title_sort impact of age on clinical outcomes among patients with hepatocellular carcinoma a systematic review and meta analysis
topic Liver cancer
Elderly
Disparities
Prognosis
Treatment
url http://www.sciencedirect.com/science/article/pii/S258955592500045X
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