Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with limited thera-peutic options and poor prognosis, underscoring the need for more effective precision medicine strategies. In this context, digital twins (DTs) and biological twins (BTs) have emerged as complementary approaches to model disease complexity and personalize treatment. DTs integrate multi-modal patient data, including imaging, clinical, and multi-omics information, into computational frameworks capable of predicting disease trajectories and therapeutic responses. BTs, such as patient-derived organoids and xenografts, enable functional validation of these predictions in patient-specific ex-perimental systems. This review synthesizes current advances in DT- and BT-based approaches in CCA, highlighting their respective strengths and limitations, and dis-cusses emerging hybrid frameworks that iteratively connect computational modeling with biological experimentation. Despite promising developments, significant chal-lenges remain, including data integration, model validation, regulatory alignment, and clinical adoption. Addressing these barriers will be critical to translating twin-based strategies into clinically actionable tools for personalized oncology.

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with limited therapeutic options and poor prognosis. The increasing complexity of molecular stratification and treatment selection has stimulated interest in computational and biological modeling approaches for precision oncology. Objective. This narrative review aims to provide a comprehensive overview of digital twins (DTs), DT-enabling computational models, and biological twins (BTs) in CCA, discussing their applications, limitations, and potential integration within hybrid precision medicine frameworks. Methods: A narrative literature review was conducted. To inform the twin-focused sections, a structured PubMed search was performed using predefined keywords related to CCA and twin-related technologies, including organoids, xenografts, organ-on-chip systems. Particular attention was devoted to recent studies addressing computational modeling, patient-derived experimental systems, and translational applications. Results: DT development in CCA is supported by an ecosystem of DT-enabling technologies, including radiomics, artificial intelligence, multi-omics integration, and simulation-based models. However, fully realized medical DTs remain unavailable. BTs, including patient-derived organoids, xenografts, and microfluidic platforms, enable functional validation of therapeutic hypotheses but face challenges related to scalability, standardization, and clinical feasibility. Emerging hybrid DT-BT frameworks seek to combine computational prediction with biological validation through iterative feedback loops, potentially improving patient stratification and treatment personalization. Conclusions: DTs and BTs represent complementary components of an evolving precision oncology ecosystem in CCA. Although technical, biological, regulatory, and implementation challenges remain, the convergence of computational models, longitudinal molecular monitoring, and patient-derived systems may facilitate clinically actionable hybrid twin frameworks. Successful translation will require both technological innovation and healthcare-system improvements to precision medicine access.

Primary biliary cholangitis (PBC) is a systemic disease in which musculoskeletal complications may impair function despite satisfactory biochemical control. This narrative review integrates PBC-specific evidence on sarcopenia, osteoporosis and osteosarcopenia with mechanistic studies of cholestasis, muscle-bone interactions and peroxisome proliferator-activated receptor (PPAR) signalling. Muscle depletion occurs before cirrhosis, but heterogeneous definitions and retrospective designs limit prevalence estimates and prognostic interpretation. Population-based studies link PBC to fractures and increased post-fracture mortality, whereas dedicated osteosarcopenia studies remain limited. Nutritional compromise, inflammation, endocrine abnormalities, symptom-related inactivity and advanced liver disease converge on the muscle-bone unit. General densitometric and fracture-risk frameworks remain necessary because PBC-specific integrated thresholds are unvalidated. PPAR agonists improve biochemical activity and, for some agents, symptoms, but their musculoskeletal effects must be considered separately by receptor isoform. Experimental oxidative adaptation and exploratory bone-density findings do not establish sarcopenia reversal or fracture protection; fracture signals and potential muscle toxicity require independent assessment. Ileal bile acid transporter inhibition offers pruritus relief but also requires attention to fat-soluble vitamins and skeletal safety. Integrated evaluation of symptoms, strength, body composition, physical performance and fracture risk may identify actionable limitations. Prospective cohorts and controlled interventions with predefined musculoskeletal endpoints are needed to establish clinically meaningful benefit.