Cancer-related pain remains undertreated despite established guidelines. In hepatocellular carcinoma (HCC), underlying chronic liver disease may amplify concerns regarding analgesic safety. We aimed to evaluate pain prevalence, analgesic use, pain-related perceptions, and educational needs among patients with HCC. We conducted a cross-sectional survey of 200 adult patients with HCC receiving systemic therapy at a tertiary referral center. A 30-item questionnaire assessed pain presence and intensity using a numeric rating scale (NRS), analgesic use patterns, liver-related safety concerns, opioid-related stigma, and educational needs. Clinical characteristics, including tumor burden and liver function, were analyzed in relation to pain and perception domains. Fifty-five patients (27.5%) reported current pain (mean NRS, 3.6 ± 2.5; mean worst pain 5.2 ± 2.8). Among them, 31 (56.3%) were using analgesics; however, 51.6% reported using them only when pain became unbearable. Misconceptions regarding analgesic safety were prevalent: 70.0% believed long-term analgesic use damages the liver, 56.0% believed analgesics are unsafe with impaired liver function, 46.5% associated opioids with addiction, and 30.0% hesitated due to the term "narcotic". These beliefs were not associated with Child-Pugh class or serum albumin level. Extrahepatic metastasis was associated with higher liver-related concern scores and a trend toward increased pain prevalence. Patients with elementary school education or less had poorer pain scale knowledge and no prior counseling. Pain undertreatment and safety-related misconceptions are common in HCC and appear independent of objective liver function. Structured, proactive education-particularly for patients with untreated pain and low educational attainment-may improve pain control in this population.

Historically, intrahepatic cholangiocarcinoma (iCCA) and combined hepatocellular-cholangiocarcinoma (cHCC-CCA) were regarded as absolute contraindications for liver transplantation (LT) due to dismal outcomes characterized by high recurrence rates and poor long-term survival in early experiences. Consequently, these malignancies have been systematically excluded from standard transplant criteria for decades. However, the landscape of transplant oncology is undergoing a significant paradigm shift, driven by a deeper understanding of tumor biology and refined patient selection strategies. Recent multicenter retrospective studies have identified a distinct subgroup of patients-specifically those with "very early" iCCA in the setting of cirrhosis-who achieve excellent post-transplant outcomes comparable to those of hepatocellular carcinoma. This evidence has prompted major international societies to update their guidelines, cautiously opening the door for LT in this selected population. Conversely, cHCC-CCA remains a diagnostic and therapeutic challenge. This narrative review critically analyzes the pivotal data driving the current paradigm shift and synthesizes the latest clinical practice guidelines to provide a contemporary roadmap for the management of iCCA and cHCC-CCA in the transplant setting.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare and highly aggressive hybrid malignancy characterized by a poor prognosis and high recurrence rates due to its dual histological nature. In the absence of established standard-of-care protocols, clinical management strategies are frequently extrapolated from the guidelines for its components, hepatocellular carcinoma and intrahepatic cholangiocarcinoma (iCCA). This review evaluates the evolving role of radiotherapy (RT) as an integral part of the multidisciplinary care for cHCC-CCA. Adjuvant RT may be considered for patients exhibiting high-risk pathological features, such as positive or close resection margins, lymphovascular invasion, and perineural invasion. For unresectable disease unfeasible for surgery or transarterial therapies, definitive RT using intensified doses, analogous to iCCA protocols, is employed to improve local control. High-precision modalities, particularly particle therapies such as proton or carbon ion RT, are emphasized as preferred options for delivering ablative doses while minimizing toxicity and preserving functional liver reserve. Furthermore, preliminary clinical evidence suggests a potential synergy between RT and immune checkpoint inhibitors, with reported cases demonstrating complete responses or successful conversion to curative-intent resection. While current evidence remains limited to retrospective cohorts and case series, the strategic integration of precision RT offers a rational pathway for optimizing outcomes in cHCC-CCA, necessitating further prospective validation.

The emergence of systemic therapies has ushered in an era of chemo-diversity for hepatocellular carcinoma, in which drug sequencing is pivotal for maximizing outcomes. Among available agents, lenvatinib is notable for its potent anti-angiogenic and immunomodulatory properties. This review proposes a structured building-block strategy for optimizing sequential drug therapy, conceptualizing each treatment line as a block that contributes cumulatively to survival, and grounding the discussion in clinical insights from lenvatinib administration. We comprehensively evaluated clinical trials, preclinical investigations, and real-world data to identify actionable approaches that enhance tolerability and prolong progression-free survival, with a particular focus on mitigating adverse events, optimizing dosing schedules, and integrating with transarterial therapies. Five refinements emerge as central to maximizing therapeutic benefit: early detection and classification of adverse events, use of supportive agents such as L-carnitine and branched-chain amino acids, structured telephone follow-up, optimization of dosing schedules, including weekend-off regimens, and strategic combination with transarterial therapy. In addition, rationale-based sequencing and clinically relevant switching criteria that extend beyond RECIST are summarized. Collectively, these measures increase the height of each therapeutic block, thereby contributing to cumulative survival within the building-block strategy. In the current era of chemo-diversity, lenvatinib remains a cornerstone agent when accompanied by these clinical refinements. The review provides a practical and conceptual framework for enhancing efficacy through structured sequencing, proactive adverse-event mitigation, and synergistic locoregional strategies, with broad applicability to real-world clinical practice.

Diabetes mellitus is a cardiometabolic risk factor associated with the development of various comorbidities and malignancies. It has a bidirectional relationship with chronic liver disease, promoting hepatic inflammation and fibrosis, which can ultimately progress to advanced liver diseases such as cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Therefore, the importance of antidiabetic treatment has been increasingly emphasized as a strategy for preventing liver-related diseases in diabetic patients. Metformin, a first-line antidiabetic agent, has been shown to be effective in improving hepatic steatosis and preventing progression to advanced liver disease. Recently updated international guidelines recommend the use of metformin as a chemopreventive agent for HCC in diabetic patients, albeit with a weak recommendation. Meanwhile, as metformin alone is often insufficient for blood glucose control and concurrent metabolic comorbidities are increasingly prevalent, new second-line antidiabetic agents have been developed: glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and dipeptidyl peptidase-4 inhibitors. These novel antidiabetic agents have demonstrated cardiovascular benefits, and protective effects on liver-related outcomes and mortality in previous studies. However, due to the limited number of studies and the variability in study populations, their effects remain inconsistent across different studies. Furthermore, there are no established therapeutic guidelines for diabetic patients with liver disease. Therefore, this review aims to examine the association between the use of novel second-line antidiabetic agents and the risk of liver-related outcomes and mortality in this population.

Hepatocellular carcinoma (HCC) presents unique challenges in both the elderly and adolescent/young adult (AYA) populations, requiring distinct management approaches. Recent epidemiological data show an increasing incidence of HCC in both age groups, with elderly cases rising significantly and AYA cases showing trends in specific regions. The clinical characteristics and treatment considerations vary substantially among these populations. Elderly patients with HCC typically present with hepatitis C virus infection, metabolic dysfunction-associated steatotic liver disease, well-differentiated tumors, and multiple comorbidities. In contrast, AYA patients with HCC often present with more aggressive tumor characteristics and predominantly with hepatitis B virus-related diseases. Treatment decisions for elderly patients with HCC require careful consideration of physiological reserves, comprehensive geriatric assessments, and potential complications. Recent studies have demonstrated that elderly patients can achieve outcomes comparable to younger patients across various treatment modalities when properly selected. While surgical outcomes are comparable to those of younger patients with proper selection, less-invasive options such as radiofrequency ablation or transarterial therapies may be more appropriate for some elderly patients. The treatment approach for AYA HCC emphasizes curative intent while considering long-term effects. AYA patients require specialized attention to their psychosocial needs, fertility preservation, and long-term health maintenance. Although data on AYA patients remain limited, they are known to have relatively favorable prognoses despite exhibiting more aggressive tumor characteristics. Management of HCC in both the elderly and AYA populations requires individualized approaches that consider age-specific factors. Both groups benefit from multidisciplinary team involvement and careful consideration of quality of life.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a dismal prognosis. Atezolizumab plus bevacizumab (atezo-bev) is the recommended palliative treatment, and approximately 10% of the patients may experience a complete response (CR), according to the mRECIST criteria. The treatment duration is until disease progression or unacceptable side effects occur. Long-term continuation can cause potential toxicities and a substantial financial burden, making early treatment discontinuation a viable option. This report describes durable CR after discontinuing atezo-bev treatment in three patients with HCC and PVTT.

Hepatocellular adenomas (HCAs) are benign monoclonal liver tumors. Advances in molecular studies have led to the identification of distinct subtypes of HCA with unique pathways, clinical characteristics, and complication risks, underscoring the need for precise diagnosis and tailored management. Malignant transformation and bleeding remain significant concerns. Imaging plays a crucial role in the identification of these subtypes, offering a non-invasive method to guide clinical decision-making. Most studies involving patients with HCAs have been conducted in Western populations; however, the number of studies focused on Asian population has increased in recent years. HCAs exhibit distinct features in Asian population, such as a higher prevalence among male patients and specific subtypes (e.g., inflammatory HCAs). Current clinical guidelines are predominantly influenced by Western data, which may not fully capture these regional differences in epidemiology and subtype distribution. Therefore, this review presents the updated molecular classification of HCAs and their epidemiologic differences between Asian and Western populations, and discuss the role of imaging techniques, particularly magnetic resonance imaging using hepatobiliary contrast agents, in classifying the subtypes and predicting the risk of hepatocellular carcinoma.