Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. The recent introduction of immune checkpoint inhibitors (ICIs) has transformed the therapeutic landscape for advanced HCC. Combination regimens such as atezolizumab plus bevacizumab, durvalumab plus tremelimumab, and nivolumab plus ipilimumab have demonstrated significant survival improvements over conventional tyrosine kinase inhibitors and have become the new standard of care. However, ICIs can trigger immune-related adverse events (irAEs) through overactivation of the immune system, affecting multiple organs including the skin, gastrointestinal tract, liver, endocrine system, lungs, and heart. Patients with HCC frequently have underlying liver diseases such as chronic hepatitis or cirrhosis, placing them at higher risk of hepatic irAEs compared to that with other cancer types, which can markedly influence prognosis. The pathophysiology of irAEs is driven by a series of interconnected immune mechanisms, including excessive T-cell activation, disruption of immune tolerance, cytokine dysregulation, complement-mediated injury, and innate immune activation. Clinical decisions regarding the continuation, interruption, or discontinuation of ICIs, as well as the administration of corticosteroids or immunosuppressants, should be guided by the severity of toxicity. Organ-specific management strategies and multidisciplinary collaboration are essential, particularly for severe presentations. This review summarizes the incidence, mechanisms, and management strategies for ICI-related irAEs in advanced HCC, and provides practical insights for clinical decision-making.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Biliary tract cancer (BTC) is a rare but highly aggressive malignancy that includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, and gallbladder cancer (GBC). While BTC has a low global incidence, its regional variations are notable. Among nations, Korea has the second-highest incidence of BTC globally, with the highest mortality rate worldwide, underscoring the need for a deeper understanding of this cancer. Liver fluke infection and hepatitis B virus infection are key risk factors unique to Korea, contributing to regional differences in BTC incidence. Additionally, genomic alterations in Korean patients with BTC differ from those in other populations, including lower frequencies of IDH1 mutations and FGFR2 fusions in ICC and a higher prevalence of ERBB2 amplification in GBC. Recognizing the clinical significance of these alterations, ivosidenib and pemigatinib have been approved in Korea for BTC patients with IDH1 mutations and FGFR2 fusions, respectively. This review explores the epidemiology, risk factors, and molecular features of BTC, along with corresponding targeted therapies. Furthermore, we compare the unique characteristics of BTC in Korea with global data to inform future research and clinical practice.

Biliary tract cancer (BTC) is a rare but highly aggressive malignancy that includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, and gallbladder cancer (GBC). While BTC has a low global incidence, its regional variations are notable. Among nations, Korea has the second-highest incidence of BTC globally, with the highest mortality rate worldwide, underscoring the need for a deeper understanding of this cancer. Liver fluke infection and hepatitis B virus infection are key risk factors unique to Korea, contributing to regional differences in BTC incidence. Additionally, genomic alterations in Korean patients with BTC differ from those in other populations, including lower frequencies of IDH1 mutations and FGFR2 fusions in ICC and a higher prevalence of ERBB2 amplification in GBC. Recognizing the clinical significance of these alterations, ivosidenib and pemigatinib have been approved in Korea for BTC patients with IDH1 mutations and FGFR2 fusions, respectively. This review explores the epidemiology, risk factors, and molecular features of BTC, along with corresponding targeted therapies. Furthermore, we compare the unique characteristics of BTC in Korea with global data to inform future research and clinical practice.

Biliary tract cancer (BTC) is a rare but highly aggressive malignancy that includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, and gallbladder cancer (GBC). While BTC has a low global incidence, its regional variations are notable. Among nations, Korea has the second-highest incidence of BTC globally, with the highest mortality rate worldwide, underscoring the need for a deeper understanding of this cancer. Liver fluke infection and hepatitis B virus infection are key risk factors unique to Korea, contributing to regional differences in BTC incidence. Additionally, genomic alterations in Korean patients with BTC differ from those in other populations, including lower frequencies of IDH1 mutations and FGFR2 fusions in ICC and a higher prevalence of ERBB2 amplification in GBC. Recognizing the clinical significance of these alterations, ivosidenib and pemigatinib have been approved in Korea for BTC patients with IDH1 mutations and FGFR2 fusions, respectively. This review explores the epidemiology, risk factors, and molecular features of BTC, along with corresponding targeted therapies. Furthermore, we compare the unique characteristics of BTC in Korea with global data to inform future research and clinical practice.

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy that ranks among the top three causes of cancer-related mortality worldwide. Although the development of systemic therapies for HCC historically lagged behind that of other solid tumors, the recent emergence of immune checkpoint inhibitors (ICIs) and targeted agents has substantially reshaped the therapeutic landscape.Current Concepts: ICI-based combination therapies, such as atezolizumab plus bevacizumab (IMbrave150), durvalumab plus tremelimumab (HIMALAYA), and nivolumab plus ipilimumab (CheckMate-9DW), have become new standards of care for first-line treatment of advanced HCC. These regimens have demonstrated superior overall survival compared with tyrosine kinase inhibitors (TKIs); however, objective response rates remain limited to approximately 20% to 30%. As treatment advances beyond the first line, TKIs including sorafenib, lenvatinib, regorafenib, and cabozantinib continue to serve as key second- or third-line options. In parallel, emerging strategies—such as salvage immunotherapy, locoregional treatment for oligoprogression, and multidisciplinary care—are receiving increasing attention.Discussion and Conclusion: Despite recent therapeutic advances, the management of advanced HCC remains challenging because of underlying liver dysfunction, marked tumor heterogeneity, and the absence of robust predictive biomarkers. Personalized treatment strategies that incorporate liver function, performance status, and comorbidities are therefore essential. Future efforts should prioritize the identification of predictive biomarkers and the development of more effective combination approaches. In addition, integrating systemic therapy with locoregional modalities and expanding access to clinical trials will be critical for improving long-term survival outcomes in this patient population.

Recent clinical outcomes of multi-regimen chemotherapy in patients with cholangiocarcinoma (CCC) have shown benefits in terms of overall survival. However, repeated endoscopic biliary drainage (EBD) and serious adverse events negatively affect prolongation of the survival period.The aim of this study was to investigate the prevalence of massive hemobilia and the outcomes of its management with fully covered self-expandable metal stents (FC-SEMSs) in patients with hilum-involving CCC receiving multi-regimen chemotherapy. The methods and effects of FCSEMS placement were retrospectively investigated following the occurrence of massive hemobilia during EBD. A total of 356 patients with CCC received multi-regimen chemotherapy. Among them, 181 patients had hilar invasion, and seven patients (3.9%) developed massive hemobilia during repeated EBD using removable stents. In all cases, the tumor encased the right hepatic artery. In six patients (85.7%), hemostasis was immediately and completely achieved by inserting one or two FC-SEMSs proximal to the hilar invasion area. Therefore, if the tumor encases the right hepatic artery, massive hemobilia is likely to occur during multi-regimen chemotherapy.Thus, prompt placement of a FC-SEMS would be an effective treatment option for massive hemobilia in patients with hilum-involving CCC.