Therapeutic Complexity in the Aging Patient: A Comparative Review of Management Strategies and Comorbidity Burdens in Hepatocellular Carcinoma and Elderly-Onset Inflammatory Bowel Disease

Abstract

Background: The management of gastrointestinal pathologies in the elderly presents a unique clinical challenge, particularly when distinguishing between chronological age and physiological frailty. This review examines two distinct but clinically overlapping conditions prevalent in aging populations: Hepatocellular Carcinoma (HCC) and Inflammatory Bowel Disease (IBD). Methods: We conducted a comprehensive review of recent literature focusing on therapeutic outcomes, safety profiles, and comorbidity interactions. The analysis centers on the Barcelona Clinic Liver Cancer (BCLC) strategy for HCC and the risk-benefit profile of biological therapies in elderly IBD patients. Results: In HCC management, evidence suggests that older age is not an independent predictor of worse survival; rather, comorbidities dictate outcomes. Advanced locoregional therapies, including Transarterial Chemoembolization (TACE) and radioembolization, show efficacy in elderly cohorts, though ischemia-induced autophagy remains a resistance mechanism. Conversely, in elderly IBD, age acts as an independent risk factor for severe infections and adverse events associated with Anti-TNF therapy. While efficacy remains comparable to younger cohorts, discontinuation rates are significantly higher due to safety concerns, including lymphoma and non-melanoma skin cancer risks. Furthermore, extra-intestinal comorbidities, specifically chronic kidney disease and metabolic disorders, significantly complicate the management of both conditions. Conclusion: Effective management of HCC and IBD in the elderly requires a paradigm shift from age-based exclusions to comorbidity-based stratification. Personalized therapeutic strategies that account for immunosenescence and renal function are essential to optimize survival and minimize iatrogenic harm in this vulnerable demographic.

Keywords:

Hepatocellular Carcinoma, Inflammatory Bowel Disease, Geriatric Gastroenterology

References

Golfieri R, Bargellini I, Spreafico C, et al. Patients with Barcelona clinic liver cancer stages B and C hepatocellular carcinoma: time for a subclassification. Liver Cancer. 2019; 8: 78-91.

Gade TPF, Tucker E, Nakazawa MS, et al. Ischemia induces quiescence and autophagy dependence in hepatocellular carcinoma. Radiology. 2017; 283: 702–710.

Li W, Ni C-F. Current status of the combination therapy of transarterial chemoembolization and local ablation for hepatocellular carcinoma. Abdom Radiol. 2019; 44: 2268–2275.

Chang PY, Chien LN, Lin YF, et al. Nonadherence of oral antihyperglycemic medication will increase risk of end-stage renal disease. Medicine. 2015; 94: e2051.

Chang PY, Lin CJ, Chen HC, et al. 23-valent pneumococcal polysaccharide vaccine and the risk of renal progression in older patients with chronic kidney disease. Prev Med. 2023; 177: 107753.

Chi NF, Chien LN, Ku HL, et al. Alzheimer disease and risk of stroke: a population-based cohort study. Neurology. 2013; 80: 705–711.

Lin LY, Warren-Gash C, Smeeth L, et al. Data resource profile: the national health insurance research database (NHIRD). Epidemiol Health. 2018; 40: e2018062.

Makary MS, Khandpur U, Cloyd JM, et al. Locoregional therapy approaches for hepatocellular carcinoma: recent advances and management strategies. Cancers. 2020; 12: 1914.

Rognoni C, Ciani O, Sommariva S, et al. Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta–analyses. Oncotarget. 2016; 7: 72343–72355.

Llovet JM, Real MI, Montaña X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002; 359: 1734–1739.

Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002; 35: 1164–1171.

Vogel A, Chan SL, Dawson LA, et al. Hepatocellular carcinoma: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2025; 36: 491-506.

Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022; 76: 681–693.

Kanneganti M, Al-Hasan M, Bourque S, et al. Older age but not comorbidity is associated with worse survival in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2024; 24: 1038–1041.

White DL, Thrift AP, Kanwal F, et al. Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012. Gastroenterology. 2000; 152: 812–820

Hruz P, Juillerat P, Kullak-Ublick G-A, Schoepfer AM, Mantzaris GJ, Rogler G. Management of the elderly inflammatory bowel disease patient. Digestion. 2020;101(Suppl. 1):105-19.

John ES, Katz K, Saxena M, Chokhavatia S, Katz S. Management of inflammatory bowel disease in the elderly. Current treatment options in gastroenterology. 2016;14:285-304.

Sousa P, Bertani L, Rodrigues C. Management of inflammatory bowel disease in the elderly: A review. Digestive and liver disease. 2023;55(8):1001-9.

Hong SJ, Katz S. The elderly IBD patient in the modern era: changing paradigms in risk stratification and therapeutic management. Therapeutic Advances in Gastroenterology. 2021;14:17562848211023399.

Kariyawasam VC, Kim S, Mourad FH, Selinger CP, Katelaris PH, Brian Jones D, et al. Comorbidities rather than age are associated with the use of immunomodulators in elderly-onset inflammatory bowel disease. Inflammatory Bowel Diseases. 2019;25(8):1390-8.

Siegel CA, Marden SM, Persing SM, Larson RJ, Sands BE. Risk of lymphoma associated with combination anti–tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: a meta-analysis. Clinical Gastroenterology and Hepatology. 2009;7(8):874-81.

Long MD, Martin CF, Pipkin CA, Herfarth HH, Sandler RS, Kappelman MD. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143(2):390-9. e1.

Beaugerie L, Brousse N, Bouvier AM, Colombel JF, Lémann M, Cosnes J, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. The Lancet. 2009;374(9701):1617-25.

Fidder H, Schnitzler F, Ferrante M, Noman M, Katsanos K, Segaert S, et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut. 2009;58(4):501-8.

Desai A, Zator ZA, de Silva P, Nguyen DD, Korzenik J, Yajnik V, et al. Older age is associated with higher rate of discontinuation of anti-TNF therapy in patients with inflammatory bowel disease. Inflammatory bowel diseases. 2013;19(2):309-15.

Cottone M, Kohn A, Daperno M, Armuzzi A, Guidi L, D'Inca R, et al. Advanced age is an independent risk factor for severe infections and mortality in patients given anti–tumor necrosis factor therapy for inflammatory bowel disease. Clinical Gastroenterology and Hepatology. 2011;9(1):30-5.

Lobatón T, Ferrante M, Rutgeerts P, Ballet V, Van Assche G, Vermeire S. Efficacy and safety of anti‐TNF therapy in elderly patients with inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2015;42(4):441-51.

M. Noor N, Bourke A, Subramanian S. Novel therapies in inflammatory bowel disease–An update for clinicians. Alimentary Pharmacology & Therapeutics. 2024;60(9):1244-60.