This systematic review and meta-analysis examined the potential causal link between coffee consumption and hepatocellular carcinoma (HCC) risk via Mendelian randomization (MR) studies.Five eligible MR studies that involved the use of analytical approaches such as inverse variance weighted (IVW), MR-Egger, and weighted median methods were included. While previous observational studies suggested a protective role of coffee, the MR-based analyses in this study did not demonstrate a statistically significant association across all methods. IVW analysis yielded an odds ratio of 0.92 (95% confidence interval, 0.58 to 1.47), indicating no significant effect. Moderate to substantial heterogeneity was observed, but no publication bias was detected. These findings suggest that the previously reported inverse association may have been overestimated due to methodological limitations in observational research. Our results emphasize the importance of using genetically informed methods to infer causality, and the results indicate that coffee consumption may not causally reduce the risk of HCC.

Direct-acting antiviral (DAA) therapy has brought a revolution to the management of chronic hepatitis C virus infection, but its role in patients with active hepatocellular carcinoma (HCC) remains controversial. Early observations suggested a high rate of HCC recurrence following DAA treatment, raising concerns about a potential oncogenic effect regarding rapid viral clearance. However, subsequent large-scale cohort studies and meta-analyses have not consistently confirmed this finding, leading to an overall neutral conclusion regarding the impact of DAA on HCC recurrence. International guidelines from organizations such as the American Gastroenterological Association, American Association for the Study of Liver Diseases, European Association for the Study of the Liver, and Korean Association for the Study of the Liver offer conflicting recommendations, underscoring the absence of a universal framework for this patient population. While the available evidence is largely heterogeneous and retrospective, current data indicate that DAA therapy can be safely integrated into HCC management without clear evidence of harm. Oncologic outcomes, particularly overall and recurrence-free survival, are most favorable when DAAs are administered in close proximity to curative procedures or in non-transplant therapeutic settings. In contrast, studies in liver transplant candidates often show a neutral effect on oncologic outcomes after adjusting for confounding variables. These findings underscore the necessity of individualized, multidisciplinary decisions based on tumor biology, hepatic reserve, and treatment intent. Prospective studies and validated biomarkers are essential to establish a more definitive framework for optimizing DAA therapy in this complex clinical context.

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.