Background/Aims: Direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus. This study investigated whether metabolic dysfunction influences the likelihood of fibrosis regression after DAA treatment in patients with chronic hepatitis C (CHC). Methods: This multicenter, retrospective study included 8,819 patients diagnosed with CHC who were treated with DAAs and achieved a sustained virological response (SVR) between January 2014 and December 2022. Fibrosis regression was defined as a 20% reduction in noninvasive surrogates for liver fibrosis, such as liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) and the fibrosis-4 (FIB-4) score. Hypercholesterolemia (h-TC) was defined as >200 mg/dL. Results: The median age of the study population was 59.6 years, with a predominance of male patients (n=4,713, 57.3%). Genotypes 1, 2, and others were confirmed in 3,872 (46.2%), 3,487 (41.6%), and 1,024 (12.2%) patients, respectively. Diabetes mellitus (DM) was present in 1,442 (17.2%) patients and the median LS was 7.50 kPa (interquartile range, 5.30–12.50). Multivariate analysis revealed that the presence of DM and pre-DAA h-TC were independently associated with a decreased probability of fibrosis regression by VCTE. Additionally, pre-DAA h-TC was independently associated with a decreased probability of fibrosis regression by the FIB-4. Conclusions Metabolic dysfunction has an unfavorable influence on fibrosis regression in patients with CHC who achieve SVR after DAA treatment.

Background/Aims: Direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus. This study investigated whether metabolic dysfunction influences the likelihood of fibrosis regression after DAA treatment in patients with chronic hepatitis C (CHC). Methods: This multicenter, retrospective study included 8,819 patients diagnosed with CHC who were treated with DAAs and achieved a sustained virological response (SVR) between January 2014 and December 2022. Fibrosis regression was defined as a 20% reduction in noninvasive surrogates for liver fibrosis, such as liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) and the fibrosis-4 (FIB-4) score. Hypercholesterolemia (h-TC) was defined as >200 mg/dL. Results: The median age of the study population was 59.6 years, with a predominance of male patients (n=4,713, 57.3%). Genotypes 1, 2, and others were confirmed in 3,872 (46.2%), 3,487 (41.6%), and 1,024 (12.2%) patients, respectively. Diabetes mellitus (DM) was present in 1,442 (17.2%) patients and the median LS was 7.50 kPa (interquartile range, 5.30–12.50). Multivariate analysis revealed that the presence of DM and pre-DAA h-TC were independently associated with a decreased probability of fibrosis regression by VCTE. Additionally, pre-DAA h-TC was independently associated with a decreased probability of fibrosis regression by the FIB-4. Conclusions Metabolic dysfunction has an unfavorable influence on fibrosis regression in patients with CHC who achieve SVR after DAA treatment.

Background/Aims: Direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus. This study investigated whether metabolic dysfunction influences the likelihood of fibrosis regression after DAA treatment in patients with chronic hepatitis C (CHC). Methods: This multicenter, retrospective study included 8,819 patients diagnosed with CHC who were treated with DAAs and achieved a sustained virological response (SVR) between January 2014 and December 2022. Fibrosis regression was defined as a 20% reduction in noninvasive surrogates for liver fibrosis, such as liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) and the fibrosis-4 (FIB-4) score. Hypercholesterolemia (h-TC) was defined as >200 mg/dL. Results: The median age of the study population was 59.6 years, with a predominance of male patients (n=4,713, 57.3%). Genotypes 1, 2, and others were confirmed in 3,872 (46.2%), 3,487 (41.6%), and 1,024 (12.2%) patients, respectively. Diabetes mellitus (DM) was present in 1,442 (17.2%) patients and the median LS was 7.50 kPa (interquartile range, 5.30–12.50). Multivariate analysis revealed that the presence of DM and pre-DAA h-TC were independently associated with a decreased probability of fibrosis regression by VCTE. Additionally, pre-DAA h-TC was independently associated with a decreased probability of fibrosis regression by the FIB-4. Conclusions Metabolic dysfunction has an unfavorable influence on fibrosis regression in patients with CHC who achieve SVR after DAA treatment.

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 firstline 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.

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 firstline 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.