Hepatocellular carcinoma with portal vein tumor thrombosis presents a significant therapeutic challenge due to its poor prognosis and limited treatment options. This review thoroughly examines diagnostic methods, including imaging techniques and classification systems such as the Japanese Vp and Cheng’s classifications, to aid in clinical decision-making. Treatment strategies encompass liver resection and liver transplantation, particularly living donor liver transplantation after successful downstaging, which have shown potential benefits in selected cases. Locoregional therapies, including hepatic arterial infusion chemotherapy, transarterial chemoembolization, transarterial radioembolization, and external beam radiation therapy, remain vital components of treatment. Recent advancements in systemic therapies, such as sorafenib, lenvatinib, and immune checkpoint inhibitors (e.g., atezolizumab plus bevacizumab) have demonstrated improvements in overall survival and progression-free survival. These developments underscore the importance of a multidisciplinary and personalized approach to improve outcomes for patients with hepatocellular carcinoma and portal vein tumor thrombosis.

Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly recognized as a leading cause of hepatocellular carcinoma (HCC), the third-leading cause of cancer mortality worldwide, driven by the global obesity epidemic. Projected to become the primary cause of HCC by 2030, MASH-HCC presents unique clinical challenges. This review examines its clinical management, including surveillance strategies and treatment advances, and discusses prospects to overcome existing challenges. MASH-HCC accounts for 10%–20% of HCC cases, particularly in Western countries, with a rising incidence due to obesity. Risk factors include cirrhosis, diabetes, obesity, alcohol, smoking, genetic polymorphisms (e.g., PNPLA3), and microbiome alterations. The pathogenesis involves fibrosis, immune dysfunction (e.g., T-cell impairment), and molecular changes. Prevention focuses on lifestyle modifications. Surveillance in patients with MASH cirrhosis is crucial but is hindered by poor ultrasound sensitivity in obese patients, necessitating alternative methods. Treatment mirrors that of other HCC types, but comorbidities and potentially reduced efficacy of immunotherapy necessitate tailored approaches. MASH is becoming the leading cause of HCC, necessitating lifestyle interventions for prevention. Improved surveillance and early detection are critical but challenging due to obesity-related factors. Treatments align with those for other HCC types, but comorbidities and potential differences in immunotherapy efficacy due to T-cell dysfunction require careful consideration. Key needs include identifying molecular drivers in non-cirrhotic metabolic dysfunction-associated steatotic liver disease, developing preventive therapies, refining surveillance methods, and tailoring treatments. Trials should specifically report MASH-HCC outcomes to enable personalized therapies. Further research is needed to understand T-cell dysfunction, optimize immunotherapies, and identify predictive biomarkers.

Hepatocellular carcinoma (HCC) remains a critical health concern in Korea, ranking as the second leading cause of cancer mortality and imposing substantial economic burdens, particularly among the working-age population. This review examines recent advancements in treating advanced HCC, referencing the updated 2022 HCC guidelines and the Barcelona Clinical Liver Cancer system. Historically, first-line systemic therapies included sorafenib and lenvatinib, with regorafenib, cabozantinib, or ramucirumab serving as second-line options. Since 2020, immune checkpoint inhibitors have shown superior overall survival than sorafenib, leading to the adoption of combination therapies such as atezolizumab with bevacizumab and durvalumab with tremelimumab as first-line treatments. The IMbrave150 study demonstrated that atezolizumab–bevacizumab significantly extended median overall survival and progression-free survival, with the longest survival reported in any phase 3 trial for advanced HCC. Similarly, the HIMALAYA study indicated that durvalumab combined with tremelimumab significantly improved survival rates. Second-line therapies now include regorafenib, cabozantinib, ramucirumab, nivolumab with ipilimumab, and pembrolizumab, each offering benefits for specific patient populations. Nonetheless, these therapies are associated with side effects that require careful management. Traditional targeted therapies can lead to hypertension, cardiovascular events, and hand-foot skin reactions, whereas immune checkpoint inhibitors may cause immune-related adverse events affecting the skin, gastrointestinal tract, and endocrine system. Clinicians must be well-versed in these treatments and their potential side effects to provide optimal patient care. The emergence of combination therapies targeting complex biological pathways signifies a new paradigm in HCC treatment, emphasizing the importance of continuous education and vigilant monitoring to optimize patient outcomes.