Validation of non-invasive diagnosis of CSPH in patients with compensated advanced chronic liver disease according to Baveno VII.

BACKGROUND AND AIMS: Baveno VII consensus introduced the non-invasive criteria of clinically significant portal hypertension (CSPH) using liver stiffness measurement (LSM). We evaluated the usefulness of the Baveno VII criteria to predict the risk of decompensation in patients with compensated advanced chronic liver disease (cACLD). METHODS: We conducted a retrospective cohort study of 1966 patients with cACLD. Patients were categorized into four groups (CSPH excluded (n = 619), grey zone (low risk of CSPH (n = 699), high risk of CSPH (n = 207)), and CSPH included (n = 441)) according to Baveno VII consensus. The risk of events was estimated using a Fine and Gray competing risk regression analysis, with liver transplantation and death as competing events. We calculated standardized hazard ratios (sHR) to assess the relative risk of decompensation. RESULTS: Among 1966 patients, 178 developed decompensations over a median follow-up of 3.06 (IQR: 1.03-6.00) years. Patients with CSPH had the highest decompensation risk, followed by the grey zone high-risk group, grey zone low-risk group, and those without CSPH with 3-year cumulative risks of 22%, 12%, 3.3%, and 1.4% respectively (p < .001). Compared to CSPH excluded group, CSPH included group (sHR: 8.00, 95% CI: 4.00-16.0), grey zone high-risk group (sHR: 6.57, 95% CI: 3.16-13.6), grey zone low-risk group (sHR: 2.15, 95% CI: 1.04-4.41) had significantly higher risk of decompensation (Gray's test p < .01). CONCLUSION: Non-invasive diagnosis of CSPH according to the Baveno VII criteria can stratify the risk of decompensation.

The Association Between Breastfeeding and Nonalcoholic Fatty Liver Disease in Parous Women: A Nation-wide Cohort Study.

BACKGROUND AND AIMS: Breastfeeding has multiple effects on maternal health outcomes. However, the effect of breastfeeding on NAFLD in parous women remains unclear. APPROACH AND RESULTS: A total of 6,893 Korean parous women aged 30-50 years who participated in the Korean National Health and Nutrition Examination Survey were assessed for the association between breastfeeding and NAFLD. Duration of lactation was calculated by dividing the total lactation period by the number of breastfed children. NAFLD was defined by the hepatic steatosis index. Of 6,893 women, 1,049 (15.2%) had NAFLD. Prevalence of NAFLD was 18.3%, 14.3%, 12.3%, 14.4%, and 15.8% in women with a breastfeeding period of <1, ≥1-<3, ≥3-<6, ≥6-<12, and ≥12 months, respectively. In a fully adjusted model, breastfeeding (≥1 month) was associated with reduced NAFLD prevalence (OR, 0.67; 95% CI, 0.51-0.89) after adjusting for metabolic, socioeconomic, and maternal risk factors. Fully adjusted ORs (95% CI) decreased with an increase of breastfeeding duration: 0.74 (0.49-1.11), 0.70 (0.47-1.05), 0.67 (0.48-0.94), and 0.64 (0.46-0.89) for women with ≥1-<3, ≥3-<6, ≥6-<12, and ≥12 months of breastfeeding duration, respectively, compared to women with <1 month of breastfeeding duration. Such an association was also observed in all predefined subgroups without interaction. CONCLUSIONS: Breastfeeding showed a protective effect against NAFLD in later life of parous women, suggesting a maternal benefit of breastfeeding on NAFLD.

Incidence and risk factors for development of hepatocellular carcinoma at young age in patients with chronic hepatitis B.

BACKGROUND: Some young adults with chronic hepatitis B virus (HBV) infection might be at high risk for hepatocellular carcinoma (HCC), enough to justify regular HCC surveillance despite the young age of the patients. However, ways to identify at-risk individuals who may benefit from HCC surveillance need further evaluations. METHODS: A hospital-based retrospective cohort of 2757 chronic HBV mono-infected young adults (median age: 34 years, males 66%) were analyzed. The primary outcome was young-onset HCC, defined as a diagnosis made under 40 years of age. We calculated the HCC incidence/1000 person-years in the overall cohort and pre-defined subgroups of patients assessed the independent risk factors that can be used to identify surveillance targets. RESULTS: The HCC incidence was low (2.55/1000 person-years) in the overall cohort. However, the HCC incidence varied widely according to baseline characteristics: lowest among young adults with FIB-4 ≤ 0.70 (0.17/1000 person-years) and highest in young adults with radiological cirrhosis (30.7/1000 person-years). In multivariable analysis, radiological cirrhosis, the FIB-4 index, and serum HBV DNA level were independent factors associated with HCC development at a young age. Performance for prediction of young-onset HCC in radiological cirrhotic patients showed the highest specificity but sensitivity was <70%. Combination with FIB-4 index and HBV DNA levels increased sensitivity to 90%. CONCLUSION: Risk stratification using FIB-4 index, HBV DNA levels, and either combining radiological cirrhosis or gender and AFP levels would be helpful to stratify young patients who would and would not benefit from regular HCC surveillance.

Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

BACKGROUND AND AIMS: Statins have pleiotropic effects that may include chemoprevention. Several observational studies have suggested that statins may prevent hepatocellular carcinoma (HCC), but they have not yet been fully studied in patients with chronic hepatitis B virus (HBV) infections. APPROACH AND RESULTS: A hospital-based retrospective cohort of 7,713 chronic HBV-infected individuals between January 2008 and December 2012 were analyzed. The primary outcome was the development of HCC. Patients who used statins for at least 28 cumulative defined daily doses during the follow-up period were defined as statin users (n = 713). The association between the use of statin and the incidence of HCC was analyzed using the multivariable Cox regression model with time-dependent covariates. During a median follow-up of 7.2 years (min-max: 0.5-9.9), HCC newly developed in 702 patients (9.1%). Statin use was associated with a lower risk of HCC (adjusted hazard ratio = 0.36, 95% confidence interval: 0.19-0.68, adjusted for age, sex, cirrhosis, diabetes, hypertension, serum alanine aminotransferase, cholesterol, HBV DNA level, antiviral treatment, and antiplatelet therapy). The observed benefit of the statin use was dose-dependent (adjusted hazard ratio [95% confidence interval], 0.63 [0.31-1.29]; 0.51 [0.21-1.25]; 0.32 [0.07,1.36]; and 0.17 [0.06, 0.48] for patients with statin use of 28-365, 366-730, 731-1095, and more than 1,095 cumulative defined daily doses, respectively). In subgroup analysis, the association between statin use and reduced risk of HCC was observed in all prespecified subgroups analyzed. CONCLUSION: Statin use was associated with a reduced risk of HCC development in chronic HBV-infected patients, suggesting that statins may have a chemopreventive role in this population. These findings warrant a prospective evaluation.

Prognosis of hepatocellular carcinoma patients diagnosed under regular surveillance: potential implications for surveillance goal.

AIMS: The goal of hepatocellular carcinoma (HCC) surveillance is to diagnose cancer at an early stage when treatment is likely to provide the best outcome and thereby, reduce mortality. However, no specific criteria define the 'early stage' for tumors diagnosed under HCC surveillance. We aimed to analyze factors that determined the outcome of HCC patients diagnosed under regular surveillance, to find out how early it is necessary to detect tumors during surveillance. METHODS: A retrospective cohort of 874 HCC patients with preserved liver function (Child-Pugh A) who were diagnosed under regular HCC surveillance at Samsung Medical Center from 2014 to 2016 and did not receive liver transplantation as an initial treatment were analyzed. The primary outcome was overall survival (OS). RESULTS: Tumor size, presence of vascular invasion, albumin-bilirubin grade, and initial treatment modality were independent factors for OS in multivariable analysis. When categorized according to the tumor size, the risk of mortality increased for tumors of > 3 cm, while tumors of 2-3 cm showed similar mortality risks as tumors of ≤2 cm. When categorized according to the tumor factors, curative-intent treatment (resection or ablation) can be applied to 84.5% with excellent outcomes (5-year OS rate, 93.4%), for tumors of ≤3 cm without vascular invasion. CONCLUSIONS: When tumors of ≤3 cm were detected and had no vascular invasion, curative-intent treatment was applied for most patients and showed excellent OS. This finding suggests that to detect tumors of <3 cm without vascular invasion may be considered as the goal of HCC surveillance.

Recurrence pattern and surveillance strategy for rectal neuroendocrine tumors after endoscopic resection.

BACKGROUND AND AIM: Endoscopic resection is highly effective treatment option for rectal neuroendocrine tumors (NETs) as they usually present as small localized tumors. However, there are no well-established surveillance strategies following endoscopic resection. We established our own protocol for the surveillance of rectal NETs after endoscopic resection since 2013. This study aimed to assess the outcome and to optimize the surveillance strategies after endoscopic resection. METHODS: We retrospectively analyzed the data of patients with endoscopically treated rectal NETs between January 2013 and April 2018 at Samsung Medical Center. We analyzed 337 patients with a median follow-up duration of 35.0 months (min-max: 12.0-88.3). RESULTS: A total of 329 (97.6%) patients had tumors ≤ 1 cm in size, and eight (2.4%) patients had tumors > 1 cm in diameter. Synchronous rectal NETs were diagnosed in nine (2.7%) patients. Thirteen (3.9%) patients were identified as having positive resection margins. Regardless of the salvage treatment, none of these patients developed recurrence. Metachronous rectal NETs were diagnosed in nine (2.7%) patients. Metachronous lesions were associated with the number of synchronous lesions at initial diagnosis (P < 0.001, hazard ratio = 1.75, 95% confidence interval = 1.38-2.23). Extracolonic metastasis was not detected in this study. CONCLUSION: Although initial screening for detecting metastatic lesions using computed tomography is recommended, repeated imaging for detecting extracolonic recurrence was not necessary for small non-metastatic rectal NETs. However, regular endoscopic follow-up seems reasonable, especially in case of synchronous rectal NETs, for detecting metachronous rectal NETs.

Different Performance of Liver Stiffness Measurement According to Etiology and Outcome for the Prediction of Liver-Related Events.

BACKGROUND/AIMS: Liver stiffness measurement (LSM) by transient elastography (TE) has shown promising results for prediction of hepatocellular carcinoma (HCC) and hepatic decompensation in patients with chronic liver disease (CLD). However, whether prognostic performance of TE differs according to etiology or type of outcome remains further clarification. METHODS: Performance of LSM for the prediction of HCC and hepatic decompensation was analyzed in a cohort of 4026 patients with asymptomatic CLD. RESULTS: During median 4.5 years of follow-up (range 3.0-6.2 years), liver-related events (LRE) were observed in 196 patients (166 with HCC, 45 with hepatic decompensation, and 15 with both). In the multivariate analysis, LSM was independent factor associated with LRE and showed high AUROC (0.78). When stratified by type of outcome and etiology of liver disease, LSM showed high AUROC for the prediction of HCC for patients with non-viral hepatitis (0.89), while it showed relatively low AUROC for the prediction of HCC for patients with viral hepatitis (0.75). For the prediction of hepatic decompensation, LSM showed high AUROC for patients with both viral- and non-viral hepatitis (0.90, 0.90, respectively). CONCLUSIONS: LSM showed powerful prognostic role for the prediction of LRE in patients with CLD. Notably, HCC risk was not negligible in patients with viral hepatitis who showed LSM value < 10 kPa, indicating watchful attention for HCC is still needed for viral hepatitis patients with low LSM.

Role of transarterial chemoembolization for hepatocellular carcinoma with extrahepatic metastases in the era of advancing systemic therapy.

Background/Aims: Systemic therapy is the current standard treatment for hepatocellular carcinoma (HCC) with extrahepatic metastases (EHM). However, some patients with HCC and EHM undergo transarterial chemoembolization (TACE) to manage intrahepatic tumors. Herein, we aimed to explore the appropriateness of TACE in patients with HCC and EHM in an era of advanced systemic therapy. Methods: This study analyzed 248 consecutive patients with HCC and EHM (median age 58.5 years, 83.5% male, and 88.7% Child-Pugh A) who received TACE or systemic therapy (83 sorafenib, 49 lenvatinib, 28 immunotherapy-based) between January 2018 and January 2021. Results: Among the patients, 196 deaths were recorded during a median follow-up of 8.9 months. Patients who received systemic therapy had a higher albumin-bilirubin grade, elevated tumor markers, an increased number of intrahepatic tumors, larger-sized tumors, and more frequent portal vein invasion than those who underwent TACE. TACE was associated with longer median overall survival (OS) than sorafenib (15.1 vs. 4.7 months; 95% confidence interval [CI]: 11.1-22.2 vs. 3.7-7.3; hazard ratio [HR] 1.97, P<0.001). After adjustment for potential confounders, TACE was associated with statistically similar survival outcomes to those of lenvatinib (median OS: 8.0 months; 95% CI: 6.5-11.0; HR 1.21, P=0.411) and immunotherapies (median OS: 14.3 months; 95% CI: 9.5-27.0; HR 1.01, P=0.973), demonstrating survival benefits equivalent to these treatments. Conclusion: In patients with HCC and EHM, TACE can provide a survival benefit comparable to that of newer systemic therapies. Accordingly, TACE remains a valuable option in this era of new systemic therapies.

Massive Transfusion Protocol and Outcome of Patients with Acute Variceal Bleeding.

Background/Aims: The massive transfusion protocol (MTP) can improve the outcomes of trauma patients with hemorrhagic shock and some patients with non-traumatic hemorrhagic shock. However, no information is available regarding whether MTP can improve the outcomes of acute variceal bleeding (AVB). This study aimed to determine the effects of MTP on the outcomes of patients with AVB. Methods: Consecutive patients (n = 218) with AVB who did not have current malignancy and visited the emergency room between July 2014 and June 2022 were analyzed. 42-day mortality and failure to control the bleeding were compared between patients with and without MTP activation. Additionally, propensity-score matching was conducted. Results: The amount of blood product transfused was higher in the MTP group. The 42-day mortality rate (42.1% vs. 1.5%, p < 0.001) and the rate of failure to control bleeding (36.8% vs. 0.5%, p < 0.001) were significantly higher in those who received blood transfusions by MTP. MTP was an independent factor associated with 42-day mortality in the multivariable-adjusted analysis (HR 21.05; 95% CI 3.07-144.21, p = 0.002, HR 24.04; 95% CI 3.41-169.31, p = 0.001). The MTP group showed consistently higher 42-day mortality and failure to control bleeding in all subgroup analyses, stratified by systolic blood pressure, hemoglobin level, and the model for end-stage liver disease score. The MTP group also showed higher 42-day mortality (42.9% vs. 0%, p = 0.001) and failure to control bleeding (42.9% vs. 0%, p = 0.001) in a propensity score-matched analysis (n = 52). Conclusions: MTP was associated with poor outcomes in patients with AVB. Further studies are needed to see whether MTP can be an option for patients with massive AVB.

Analysis of Factors Predicting the Real-World Efficacy of Atezolizumab and Bevacizumab in Patients with Advanced Hepatocellular Carcinoma.

Background/Aims: Atezolizumab and bevacizumab have shown promising results for the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials. In this study, the real-world efficacy and safety of atezolizumab and bevacizumab in treating advanced HCC were evaluated. Methods: In this retrospective study of patients at a Korean tertiary cancer center, 111 patients with Barcelona Clinic Liver Cancer stage B or C HCC received atezolizumab and bevacizumab as first-line therapy from May 2022 to June 2023. We assessed the progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events. Results: Patients with Barcelona Clinic Liver Cancer stage C HCC and Child-Pugh class A liver function were included in the study. The median PFS was 6.5 months, with an ORR of 27% and a DCR of 63%. Several factors, including the albumin-bilirubin grade, age, C-reactive protein and α-fetoprotein in immunotherapy score, macrovascular invasion, lung metastases, and combined radiotherapy, were found to significantly influence PFS (p<0.05). Patients with peritoneal seeding showed an higher ORR. The safety profile was consistent with that observed in clinical trials. Conclusions: Atezolizumab and bevacizumab demonstrated real-world efficacy in the treatment of advanced HCC, with ORRs and DCRs aligning with those observed in clinical trials. Variations in PFS and ORR based on specific risk factors highlight the potential of atezolizumab and bevacizumab in precision medicine for advanced HCC.

Prevalence and predictors of multidrug-resistant bacteremia in liver cirrhosis.

BACKGROUND/AIMS: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. METHODS: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. RESULTS: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). CONCLUSION: More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

Hepatocellular carcinoma outcomes and potential implications for surveillance in elderly patients.

International liver societies recommend hepatocellular carcinoma (HCC) surveillance for those at high-risk of developing HCC. While previous studies have shown the benefits of surveillance for middle-aged patients, but its necessity for elderly patients is unclear. This study aimed to assess the benefits of HCC surveillance in the elderly by comparing diagnosis mode of HCC. Consecutive, elderly patients aged 75 years or older who were newly diagnosed with HCC were screened at our institution between January 2009 and December 2021. Patients were grouped into those who were diagnosed with HCC during surveillance (n = 235, surveillance group) and those who were diagnosed with HCC due to symptoms (n = 184, symptomatic group). The study outcome was overall survival. It was compared in the overall cohort and a propensity score (PS)-matched cohort. Early-stage diagnosis was more frequent in the surveillance group than in the symptomatic group (mUICC stage I/II: 72.3% vs. 39.1%, p < 0.001). The overall survival rate was better in the surveillance group than in the symptomatic group (median 4.4 vs. 2.1 years, log-rank p < 0.001). In multivariable-adjusted models, the hazard ratio (HR) of mortality of the surveillance group compared to the symptomatic group was 0.64 (95% confidence interval (CI): 0.47-0.87). However, further adjustment for the tumor stage markedly attenuated this association, which was no longer statistically significant (adjusted HR = 0.75; 95% CI: 0.54-1.02). In the PS-matched cohort analysis, outcomes were similar when the PS matching variables included the tumor stage. In contrast, when PS matching variables did not include the tumor stage, outcomes were better for the surveillance group. The surveillance group of elderly patients showed better survival than the symptomatic group, which was largely explained by earlier tumor stage at diagnosis. This suggests that the overall outcome of elderly HCC patients could be improved by increasing surveillance-detected cases compared to symptom-driven cases.

Machine learning-based clinical decision support system for treatment recommendation and overall survival prediction of hepatocellular carcinoma: a multi-center study.

The treatment decisions for patients with hepatocellular carcinoma are determined by a wide range of factors, and there is a significant difference between the recommendations of widely used staging systems and the actual initial treatment choices. Herein, we propose a machine learning-based clinical decision support system suitable for use in multi-center settings. We collected data from nine institutions in South Korea for training and validation datasets. The internal and external datasets included 935 and 1750 patients, respectively. We developed a model with 20 clinical variables consisting of two stages: the first stage which recommends initial treatment using an ensemble voting machine, and the second stage, which predicts post-treatment survival using a random survival forest algorithm. We derived the first and second treatment options from the results with the highest and the second-highest probabilities given by the ensemble model and predicted their post-treatment survival. When only the first treatment option was accepted, the mean accuracy of treatment recommendation in the internal and external datasets was 67.27% and 55.34%, respectively. The accuracy increased to 87.27% and 86.06%, respectively, when the second option was included as the correct answer. Harrell's C index, integrated time-dependent AUC curve, and integrated Brier score of survival prediction in the internal and external datasets were 0.8381 and 0.7767, 91.89 and 86.48, 0.12, and 0.14, respectively. The proposed system can assist physicians by providing data-driven predictions for reference from other larger institutions or other physicians within the same institution when making treatment decisions.

Radiotherapy trend in elderly hepatocellular carcinoma: retrospective analysis of patients diagnosed between 2005 and 2017.

PURPOSE: To report the trends of radiotherapy in the management of elderly patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We retrospectively reviewed patients who entered HCC registry of Samsung Medical Center between 2005 and 2017. Patients who were 75 years or older at the time of registration were defined as elderly. They were categorized into three groups based on the year of registration. Radiotherapy characteristics were compared between the groups to observe differences by age groups and period of registration. RESULTS: Out of 9,132 HCC registry patients, elderly comprised 6.2% (566 patients) of the registry, and the proportion increased throughout the study period (from 3.1% to 11.4%). Radiotherapy was administered to 107 patients (18.9%) in elderly group. Radiotherapy utilization in the early treatment process (within 1 year after registration) has rapidly increased from 6.1% to 15.3%. All treatments before 2008 were delivered with two-dimensional or three-dimensional conformal radiotherapy, while more than two-thirds of treatments after 2017 were delivered with advanced techniques such as intensity-modulated radiotherapy, stereotactic body radiotherapy, or proton beam therapy. Overall survival (OS) of elderly was significantly worse than younger patients. However, for patients who received radiotherapy during the initial management (within one month after registration), there was no statistically significant difference in OS between age groups. CONCLUSION: The proportion of elderly HCC is increasing. Radiotherapy utilization and adoption of advanced radiotherapy technique showed a consistently increasing trend for the group of patients, indicating that the role of radiotherapy in the management of elderly HCC is expanding.

Nomogram for predicting overall survival in patients with large (>5 cm) hepatocellular carcinoma based on real-world practice.

BACKGROUND/AIM: Patients with large (>5 cm) hepatocellular carcinoma (HCC) have limited treatment options, thus necessitating the identification of prognostic factors and the development of predictive tools. This study aimed to identify prognostic factors and to construct a nomogram to predict survival outcomes in patients with large HCC. METHODS: A cohort of 438 patients, who were diagnosed with large HCC at a tertiary hospital between 2015 and 2018, was analyzed. Cox proportional hazards models were used to identify key prognosticators of overall survival (OS), and an independent set of prognostic factors was used to develop a nomogram. The discrimination and calibration abilities of the nomogram were assessed and internal validation was performed using cross-validation and bootstrapping methods. RESULTS: During a median follow-up of 9.3 months, the median OS was 9.9 months, and the 1-year OS rate was 43.9%. Multivariable Cox regression analysis revealed that performance status, modified albumin-bilirubin grade, tumor size, extent of portal vein tumor thrombosis, and initial treatment significantly affected OS. The newly developed nomogram incorporating these variables demonstrated favorable accuracy (Harrell's concordance index, 0.807). CONCLUSIONS: The newly developed nomogram facilitated the estimation of individual survival outcomes in patients with large HCC, providing an acceptable level of accuracy.

Clinical practice guideline and real-life practice in hepatocellular carcinoma: A Korean perspective.

Hepatocellular carcinoma (HCC) is a major cause of death in many countries, including South Korea. To provide useful and sensible advice for clinical management of patients with HCC, the Korean Liver Cancer Association and National Cancer Center Korea Practice Guideline Revision Committee have recently revised the practice guidelines for HCC management. However, there are some differences between practice guidelines and real-life clinical practice. In this review, we describe some key recommendations of the 2022 version of practice guidelines and the real-life clinical situation in South Korea, together with discussion about efforts needed to reduce the difference between guidelines and real-life clinical practice.

Metabolic dysfunction-associated fatty liver disease and the risk of hepatocellular carcinoma.

Background & Aims: The metabolic dysfunction-associated fatty liver disease (MAFLD) is a new inclusive term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analysed whether hepatocellular carcinoma (HCC) risk differs by MAFLD or NAFLD status in a large sample of asymptomatic adults. Methods: A cohort comprising 73,691 adults were followed up for the development of HCC. NAFLD was diagnosed among participants without other liver diseases (n = 65,992). Results: Participants with MAFLD showed higher incidence of HCC than those without MAFLD (0.37 and 0.24 per 1,000 person-years, respectively; p = 0.006). However, MAFLD was not an independent factor associated with HCC in multivariable adjusted analysis (hazard ratio [HR] 1.21; 95% CI 0.92-1.60). When stratified according to presence of other liver diseases, MAFLD was not associated with HCC in participants with other liver diseases. In participants without other liver diseases, both MAFLD (adjusted HR 1.84; 95% CI 1.09-3.11) and NAFLD (adjusted HR 1.71; 95% CI 1.01-2.90) were independent factors associated with HCC. When stratified according to NAFLD and MAFLD status, there was no HCC development among participants with NAFLD only during 8,936 person-years of follow-up, but this NAFLD-only group comprised 3.4%, and the majority of participants with hepatic steatosis fulfilled both NAFLD and MAFLD criteria. Conclusions: In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. For those without other chronic liver diseases, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC. Impact and Implications: This study investigated the usefulness of newly proposed nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), over non-alcoholic fatty liver disease (NAFLD), in terms of predicting hepatocellular carcinoma. In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. However, for those without chronic liver disease, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC.

External validation of subclassification system and progression pattern analysis in hepatocelluar carcinoma with macroscopic vascular invasion.

BACKGROUND AND PURPOSE: The present study aimed to validate the performance of a previously proposed subclassification model to predict prognosis after combined transarterial chemoembolization (TACE) and external beam radiotherapy (RT) for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) in an independent cohort that received the same first-line treatment for the patients with the similar disease extent characteristics, and analyzed the progression patterns as well as progression-free survival (PFS). MATERIALS AND METHODS: This study was conducted using prospectively collected data from the XXXXX HCC registry for newly diagnosed, previously untreated HCC between 2005 and 2018. Finally, 417 patients who satisfied the eligibility criteria were included and analyzed. RESULTS: The median PFS and overall survival (OS) were 5.2 and 13.9 months, respectively. Similar to a previous study, subclassification of patients into very low-, low-, intermediate-, and high-risk groups showed a median OS of 98.4, 18.3, 9.7, and 5.8 months, respectively (P < 0.001). Additionally, subclassification of patients into the very low-, low-, intermediate-, and high-risk groups showed median PFS of 18.7, 6.7, 3.3, and 2.3 months, respectively (p < 0.001). Overall, intrahepatic progression was the most common pattern of progression; however, extrahepatic progression was more common in the intermediate- and high-risk groups. CONCLUSION: The previously proposed subclassification model was successfully validated in an independent cohort. Treatment modification should be considered in the intermediate- and high-risk patient groups because of their frequent extrahepatic as well as intrahepatic progressions after combined TACE and RT.