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Patients with chronic hepatitis C virus (HCV) infection risk complications of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Previously, our proteomic examination of hepatocytes carrying a HCV-replicon revealed that deregulation of cytoskeletal dynamics may be a potential mechanism of viral-induced HCC growth. Here, we demonstrate the effect of HCV replication on the microtubule regulator stathmin (STMN1) in HCC cells. We further explore how the altered activity or synthesis of stathmin affects cellular proliferation and sensitivity to apoptosis in control HCC cells (Huh7.5) and experimental HCV-replicon harboring HCC cells (R-Huh7.5). The HCV-replicon harboring HCC cells (R-Huh 7.5) lack viral structural genes/proteins for acute infectivity and thus is the standard model for in vitro chronic infection study. Knockdown of endogenous stathmin reduced sensitivity to apoptosis in replicon cells. Meanwhile, constitutively active stathmin increased sensitivity to apoptosis in replicon cells. In addition, overexpression of constitutively active stathmin reduced cell proliferation in both control and replicon cells. These findings implicate, for the first time, a novel role for stathmin in viral replication-related apoptosis. Stathmin's potential role in HCV replication and HCC make it a candidate for the future study of viral-induced malignancies.

Background: LI‐RADS version 2018 (v2018) is used for non‐invasive diagnosis of hepatocellular carcinoma (HCC). A recently proposed modification (known as mLI‐RADS) demonstrated improved sensitivity while maintaining specificity and positive predictive value (PPV) of LI‐RADS category 5 (definite HCC) for HCC. However, mLI‐RADS requires multicenter validation. Purpose: To evaluate the performance of v2018 and mLI‐RADS for liver lesions in a large, heterogeneous, multi‐national cohort of patients at risk for HCC. Study Type: Systematic review and meta‐analysis using individual participant data (IPD) [Study Protocol: https://osf.io/duys4]. Population: 2223 observations from 1817 patients (includes all LI‐RADS categories; females = 448, males = 1361, not reported = 8) at elevated risk for developing HCC (based on LI‐RADS population criteria) from 12 retrospective studies. Field Strength/Sequence: 1.5T and 3T; complete liver MRI with gadoxetate disodium, including axial T2w images and dynamic axial fat‐suppressed T1w images precontrast and in the arterial, portal venous, transitional, and hepatobiliary phases. Diffusion‐weighted imaging was used when available. Assessment: Liver observations were categorized using v2018 and mLI‐RADS. The diagnostic performance of each system's category 5 (LR‐5 and mLR‐5) for HCC were compared. Statistical Tests: The Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS‐2 was applied to determine risk of bias and applicability. Diagnostic performances were assessed using the likelihood ratio test for sensitivity and specificity and the Wald test for PPV. The significance level was P < 0.05. Results: 17% (2/12) of the studies were considered low risk of bias (244 liver observations; 164 patients). When compared to v2018, mLR‐5 demonstrated higher sensitivity (61.3% vs. 46.5%, P < 0.001), similar PPV (85.3% vs. 86.3%, P = 0.89), and similar specificity (85.8% vs. 90.8%, P = 0.16) for HCC. Data Conclusion: This study confirms mLR‐5 has higher sensitivity than LR‐5 for HCC identification, while maintaining similar PPV and specificity, validating the mLI‐RADS proposal in a heterogeneous, international cohort. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A). Materials and methods: The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS). Results: The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group. Conclusion: RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function. Clinical relevance statement: This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas. Key Points: • The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. • Overall survival rate was significantly higher in the RFA group. • The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups. [ABSTRACT FROM AUTHOR]

Introduction: Despite the emergence of atezolizumab and bevacizumab (A + B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A + B treatment. Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A + B regimen from September 2020 to December 2022. Patients were categorized into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs. Results: This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: group 1 (n = 84) had no irAEs, group 2 (n = 37) had mild irAEs (grade 1-2), and group 3 (n = 29) had severe irAEs (grade ≥3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to group 1 (9.5 months) and group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both group 1 and group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS. Conclusion: Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A + B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis. [ABSTRACT FROM AUTHOR]

ObjectiveTo compare the conspicuity of hepatocellular carcinoma (HCC) on hepatobiliary phase of gadoxetate disodium-enhanced vs. delayed phase of gadodiamide-enhanced MR images, relative to liver function.Methods and materialsWe retrospectively identified 86 patients with newly diagnosed HCC between 2010 and 2013 and recorded the severity of liver disease by Child-Pugh class (CPC). 38 patients had gadodiamide-enhanced 5-min delayed and 48 had gadoxetate disodium-enhanced 20-min delayed hepatobiliary MR images. The conspicuity of 86 HCCs (mean size, 2.7 cm) was graded visually on a 3-point scale and quantified by liver-to-tumor contrast ratios (LTC). The relative liver parenchymal enhancement (RPE) was measured. For different CPCs, we compared the conspicuity of HCC and RPE between gadodiamide and gadoxetate.ResultsIn patients with CPC A, the visual conspicuity and LTC of the 27 HCCs imaged with gadodiamide were significantly lower than those of the 38 HCCs with gadoxetate (P

Objectives To evaluate the safety and effectiveness of chemoembolization for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) confined to a monosegment of the liver. Methods A total of 192 treatment-naive patients who received chemoembolization between March 2008 and January 2023 as a first-line treatment for locally advanced HCC with PVTT limited to a monosegment were retrospectively analysed. Overall survival (OS) and the identification of pretreatment risk factors related to OS were investigated using Cox regression analysis. Complications, radiologic tumour response, and progression-free survival (PFS) following chemoembolization were investigated. Results After chemoembolization, the 1-, 3-, and 5-year OS rates were 86%, 48%, and 39%, respectively, and the median OS was 33 months. Multivariable analyses revealed four significant pretreatment risk factors: infiltrative HCC (P  = .02; HR, 1.60), beyond the up-to-11 criteria (P  = .002; HR, 2.26), Child-Pugh class B (P  = .01; HR, 2.35), and serum AFP ≥400 ng/mL (P  = .01; HR, 1.69). The major complication rate was 5%. Of the 192 patients, 1 month after chemoembolization, 35% achieved a complete response, 47% achieved a partial response, 11% had stable disease, and 7% showed progressive disease. The median PFS after chemoembolization was 12 months. Conclusions Chemoembolization shows high safety and efficiency, and contributes to improved survival in patients with HCC with PVTT confined to a monosegment. Four risk factors were found to be significantly associated with improved survival rates after chemoembolization in patients with HCC with PVTT confined to a monosegment. Advances in knowledge (1) Although systemic therapy with a combination of atezolizumab and bevacizumab (Atezo-Bev) is recommended as the first-line treatment when HCC invades the portal vein, chemoembolization is not infrequently performed in HCC cases in which tumour burden is limited. (2) Our study cohort (n =192) had a median OS of 33 months and a 5% major complication rate following chemoembolization, findings in the range of candidates typically accepted as ideal for chemoembolization. Thus, patients with HCC with PVTT confined to a monosegment may be good candidates for first-line chemoembolization. [ABSTRACT FROM AUTHOR]

Simple Summary: This multicenter cohort study is the first to compare the clinical outcomes between the Atezolizumab-plus-bevacizumab (Ate/Bev) and transarterial-chemoembolization-plus-radiotherapy (TACE + RT) therapies in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) who had no metastasis. Through detailed analyses, our study revealed that the Ate/Bev treatment provided superior one-year survival compared to the TACE + RT treatment. The superior outcome of the Ate/Bev therapy was constantly observed in patients with an extensive HCC burden. Meanwhile, patients with unilobar disease demonstrated comparable outcomes between the two treatment groups. Finally, in the propensity score-matching analysis, both one-year survival and progression-free survival rates were higher in the Ate/Bev treatment group. These results suggest that Ate/Bev treatment should be considered as the primary treatment option for HCC patients with PVTT. With respect to TACE + RT, this could also be considered as an alternative treatment option alongside Ate/Bev therapy in patients with unilobar intrahepatic HCC. This study aimed to compare the treatment outcomes of atezolizumab-plus-bevacizumab (Ate/Bev) therapy with those of transarterial chemoembolization plus radiotherapy (TACE + RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and without metastasis. Between June 2016 and October 2022, we consecutively enrolled 855 HCC patients with PVTT. After excluding 758 patients, 97 patients (n = 37 in the Ate/Bev group; n = 60 in the TACE + RT group) were analyzed. The two groups showed no significant differences in baseline characteristics and had similar objective response and disease control rates. However, the Ate/Bev group showed a significantly higher one-year survival rate (p = 0.041) compared to the TACE + RT group, which was constantly displayed in patients with extensive HCC burden. Meanwhile, the clinical outcomes were comparable between the two groups in patients with unilobar intrahepatic HCC. In Cox-regression analysis, Ate/Bev treatment emerged as a significant factor for better one-year survival (p = 0.049). Finally, in propensity-score matching, the Ate/Bev group demonstrated a better one-year survival (p = 0.02) and PFS (p = 0.01) than the TACE + RT group. In conclusion, Ate/Bev treatment demonstrated superior clinical outcomes compared to TACE + RT treatment in HCC patients with PVTT. Meanwhile, in patients with unilobar intrahepatic HCC, TACE + RT could also be considered as an alternative treatment option alongside Ate/Bev therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: In unresectable hepatocellular carcinoma (HCC), the use of definitive radiation therapy (RT) as a combined locoregional therapeutic strategy has been increasing. Distant metastasis (DM) is one of the main causes of the declining quality of life and survival rates in the majority of cancer patients, necessitating the clinical research of key DM indicators. On the other hand, various serum biomarkers and indices of immune and inflammatory status have been investigated. This study aimed to investigate whether serum immune and inflammatory parameters can help to predict DM in HCC. In our comprehensive evaluation, the highest value of the posttreatment platelet-to-lymphocyte ratio and the lowest value of the posttreatment prognostic nutritional index were significant independent prognostic indicators of distant control and overall survival rates, respectively. Future research is necessary to confirm our findings. Background: We sought to investigate whether serum immune and inflammatory parameters can help to predict distant metastasis (DM) in patients with unresectable hepatocellular carcinoma (HCC) undergoing curative radiation therapy (RT). Methods: A total of 76 RT courses were analyzed. The following variables were included in the analysis: systemic inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), absolute lymphocyte count, lymphocyte-to-monocyte ratio, albumin, albumin-to-alkaline phosphatase ratio, RT-related parameters, and levels of total protein, hemoglobin, α-fetoprotein, and PIVKA-II. Distant control (DC) and overall survival (OS) rates were calculated and compared. Results: The mean age was 61.4 years, and most patients were men (n = 62, 81.6%). The median RT fraction number and fractional doses were 12 (range, 4–30) and 5 (range, 2–12) Gy, respectively. With a median follow-up of 12 (range, 3.1–56.7) months, the 1-year DC and OS rates were 64.4% and 55.2%, respectively. The development of DM significantly deteriorated OS (p = 0.013). In the multivariate analysis, significant independent prognostic indicators for DC and OS rates were the highest posttreatment PLR (≤235.7 vs. >235.7, p = 0.006) and the lowest posttreatment PNI (≤25.4 vs. >25.4, p < 0.001), respectively. Conclusions: Posttreatment serum PLR might be helpfully used as a predictive biomarker of DM in unresectable HCC patients undergoing RT. Future research is necessary to confirm our findings. [ABSTRACT FROM AUTHOR]

Background and Aims: Multiple arterial‐phase magnetic resonance imaging (MA‐MRI) was introduced to overcome the limitations of gadoxetic acid‐enhanced MRI, but its clinical impacts on hepatocellular carcinoma (HCC) diagnosis have not been well assessed. We investigated whether MA‐MRI with gadoxetic acid could improve the diagnosis of HCC ≤3.0 cm in comparison with single arterial‐phase MRI (SA‐MRI). Methods: This retrospective study included 397 patients from two tertiary institutions who underwent gadoxetic acid‐enhanced MRI (243 patients with 271 lesions in cohort‐1 underwent SA‐MRI, and 154 patients with 166 lesions in cohort‐2 underwent MA‐MRI). The patients had 437 hepatic lesions ≤3.0 cm with pathologic confirmation. The arterial‐phase image quality and diagnostic performance of SA‐MRI and MA‐MRI were analysed and compared. To minimize the effects of selection bias because of potential confounding between the two groups, propensity score‐matching was additionally performed. Results: MA‐MRI showed a significantly higher percentage of optimal arterial‐phase timing (94.2% vs. 74.5%, p <.001) and lower incidence of inadequate examinations (1.3% vs. 5.8%, p =.034) than SA‐MRI. MA‐MRI had a significantly higher non‐rim arterial‐phase hyperenhancement (APHE) detection rate (94.9% vs. 85.5%, p =.005) and sensitivity for diagnosing HCC (87.4% vs. 70.0%, p <.001) than SA‐MRI, but no significant difference in specificity (92.9% vs. 93.1%, p =.966). In 123 pairs of propensity score‐matched patients, MA‐MRI had significantly higher sensitivity (89.1% vs. 74.5%, p =.006) than SA‐MRI with equal specificity (92.3% vs. 92.3%, p >.999). Conclusions: Compared with SA‐MRI, MA‐MRI with gadoxetic acid can detect more non‐rim APHE and significantly improve sensitivity for diagnosing HCC ≤3.0 cm, without a significant decrease in specificity. [ABSTRACT FROM AUTHOR]

Simple Summary: G protein–coupled receptors (GPCRs) are the most critical protein group for drug development, targeting about 35% of approved drugs. As their abnormal activation causes many diseases, including cancer, it is beneficial to discover novel GPCRs that are aberrantly expressed in cancer and function in cancer progression. We discovered that neuropeptide FF receptor 2 (NPFFR2) is aberrantly expressed in liver cancer and promotes malignancy by enhancing the activity of RhoA/YAP, and inhibiting NPFFR2 dramatically reduced the malignant phenotypes. We expect that these findings provide a novel potential target for cancer treatment. G protein–coupled receptors (GPCRs) are a diverse family of cell surface receptors implicated in various physiological functions, making them common targets for approved drugs. Many GPCRs are abnormally activated in cancers and have emerged as therapeutic targets for cancer. Neuropeptide FF receptor 2 (NPFFR2) is a GPCR that helps regulate pain and modulates the opioid system; however, its function remains unknown in cancers. Here, we found that NPFFR2 is significantly up-regulated in liver cancer and its expression is related to poor prognosis. Silencing of NPFFR2 reduced the malignancy of liver cancer cells by decreasing cell survival, invasion, and migration, while its overexpression increased invasion, migration, and anchorage-independent cell growth. Moreover, we found that the malignant function of NPFFR2 depends on RhoA and YAP signaling. Inhibition of Rho kinase activity completely restored the phenotypes induced by NPFFR2, and RhoA/F-Actin/YAP signaling was controlled by NPFFR2. These findings demonstrate that NPFFR2 may be a potential target for the treatment of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to compare the performance of gadoxetic acid‐enhanced abbreviated MRI (AMRI)‐based surveillance and ultrasound‐only surveillance in high‐risk patients for hepatocellular carcinoma (HCC). Methods: Prospectively recruited high‐risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid‐enhanced MRI (CMRI) and ultrasound at 6‐months intervals were retrospectively analysed. AMRI consisted of diffusion‐weighted, T2‐weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI‐only (AAA), and ultrasound‐only (US) were compared using generalized estimating equations. Image quality was assessed. Results: In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early‐stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% [12/43]; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% [967/1012]; P = 0.01) and not significantly different from US (96.3% [975/1012]; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% [1004/1055]; P = 0.01) and the US approach (93.6% [987/1055]; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach. Conclusions: In high‐risk patients, AMRI‐based surveillance approaches had higher sensitivities than ultrasound‐only surveillance for early‐stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI‐only or ultrasound‐only approach. [ABSTRACT FROM AUTHOR]

Background and Aims: We assessed the imaging outcomes of Liver Imaging Reporting and Data System (LI‐RADS) v2018 categories in prospective hepatocellular carcinoma (HCC) surveillance cohort and determined imaging features significantly predictive of progression to a malignant LI‐RADS category. Methods: The imaging outcomes of 120 patients (162 observations) prospectively enrolled between November 2011 and August 2012 were analysed according to LI‐RADS v2018. Cumulative incidences for progression to a malignant category (LR‐5 or LR‐M) and LR‐4 or higher were calculated for each baseline category and compared using log‐rank tests. Clinical variables and imaging features significantly predictive of progression to a malignant category were evaluated using Cox proportional hazards modelling. Results: The 162 observations were initially categorized into 60 LR‐2, 75 LR‐3 and 27 LR‐4. For LR‐4 observations, the 1‐year, 3‐year and 5‐year cumulative incidences of progression to a malignant category were 18.5% (95% confidence interval, 6.6–35.2%), 43.0% (23.1–61.5%) and 52.5% (25.9–73.5%), which were significantly higher than those of LR‐2 and LR‐3 (p <.001). For LR‐3, the 1‐year, 3‐year and 5‐year cumulative incidences of progression to LR‐4 or higher were 4.1% (1.1–10.4%), 13.9% (6.7–23.6%) and 23.1% (12.7–35.4%), which were significantly higher than that of LR‐2 (p =.009). In multivariable analysis, size ≥1.0 cm (hazard ratio [HR] = 2.58, 1.04–6.40) and nonrim arterial‐phase hyperenhancement (HR = 2.45, 1.11–5.42) were significantly independently associated with progression to a malignant category. Conclusion: Long‐term imaging outcomes differed significantly according to LI‐RADS category. Size ≥1.0 cm and nonrim arterial‐phase hyperenhancement were imaging features significantly predictive of progression to a malignant category. [ABSTRACT FROM AUTHOR]

Background: Current major guidelines for diagnosis of hepatocellular carcinoma (HCC) based on imaging findings are different from each other and do not include clinical risk factors as a diagnostic criteria. Purpose: To developed and validated a new diagnostic score system using MRI and clinical features as applied in chronic hepatitis B patients. Study Type: Retrospective observational study. Subject: A total of 418 treatment‐naïve patients (out of 902 patients) with chronic hepatitis B having 556 lesions suspected for HCC which were eligible for curative treatment. Field Strength/sequence: T1W GRE in‐ and opposed‐phase, T2W FSE, DWI, and T1W 3D‐GRE dynamic contrast‐enhanced sequences at 1.5 T and 3 T. Assessment: Six radiologists with 7–22 years of experience independently evaluated MR images based on Liver Imaging Reporting and Data System (LI‐RADS) version 2018. Statistical Tests: Based on logistic regression analysis of MRI features and clinical factors, a risk score system was devised in derivation cohorts (268 patients, 352 lesions) and externally validated (150 patients, 204 lesions). The performance of the new score system was assessed by Harell's c‐index. Using cutoff value of 12, maintaining positive predictive value ≥95%, the diagnostic performances of the score system were compared with those of LR‐5. Results: The 15‐point diagnostic scoring system used MRI features (lesion size, nonrim arterial phase hyperenhancement, portal venous phase hypointensity, hepatobiliary phase hypointensity, and diffusion restriction) and clinical factors (alpha‐fetoprotein and platelet). It showed good discrimination in the derivation (c‐index, 0.946) and validation cohorts (c‐index, 0.907). Using a risk score of 12 as a cut‐off, this system yielded higher sensitivity than LR‐5 (derivation cohort, 76.8% vs. 52.1%; validation cohort, 73.4% vs. 49.5%) without significant decrease in specificity (derivation cohort, 93.1% vs. 97.2%, P = 0.074; validation cohort, 91.7% vs. 96.1%, P = 0.299). Data Conclusion: A new score system showed improved sensitivity in chronic hepatitis B patients compared to LI‐RADS without significant compromise in specificity. Evidence Level: 3 Technical Efficacy: Stage 2. [ABSTRACT FROM AUTHOR]

Background/aim: In a randomized controlled trial, lenvatinib was non-inferior to sorafenib in overall survival (OS) of patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to compare the effects of sorafenib and lenvatinib as first-line systemic therapy against uHCC with real-world data in chronic hepatitis B patients.Methods: This retrospective single-center study involved 132 patients with HBV-related uHCC. Propensity score matching (PSM) was used to balance the baseline characteristics, including age, sex, serum alpha-fetoprotein levels, Child-Pugh class, tumor size, and tumor stage. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), time to progression (TTP), and tumor response.Results: After PSM, the final analysis included 44 patients treated with lenvatinib and 88 with sorafenib. The OS (7.0 vs 9.2 months, p = 0.070) and PFS (4.6 vs 2.4 months, p = 0.134) were comparable between the two drugs. Multivariable analysis showed that lenvatinib and sorafenib were not independent prognostic factors of OS (adjusted hazard ratio = 1.41, 95% confidence interval = 0.96-2.08, p = 0.077) after adjustment for baseline alpha-fetoprotein levels, total bilirubin levels, alanine aminotransferase level, performance status, tumor stage, and tumor size. However, the lenvatinib group had a significantly prolonged TTP (5.2 vs 2.5 months, p = 0.018) and a higher objective response rate (18.2% vs 4.5%, p = 0.020) and disease control rate (77.3% vs 47.7%, p = 0.001) than the sorafenib group.Conclusions: Our study demonstrated that lenvatinib had a comparable OS and PFS but longer TTP and better tumor response compared to sorafenib in patients with HBV-related uHCC. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated the radiologic response rate of combined transarterial chemoembolization (TACE) plus radiotherapy (RT) in treatment-naïve patients with liver-confined hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI) and analyzed its clinical importance in overall survival (OS) outcomes. Methods: Patients who were treated with TACE plus RT as a first-line treatment for HCC with MVI between January 2010 and December 2015 were retrospectively reviewed. Radiologic response was assessed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 2 and 4 months after completion of RT. Landmark analysis at 2 and 4 months, and time-dependent Cox regression analysis using response as a time-dependent covariate were performed for univariable and multivariable analyses. Results: The 2-month landmark analysis included 427 patients, and the 4-month landmark analysis included 355 patients after excluding patients without imaging studies for response evaluation at 4 months. Radiologic responses were observed in 210 (49.2%) patients at 2 months and 181 (51.8%) patients at 4 months. In multivariable analyses, radiologic response was identified as an independent prognosticator for OS at 2 months (median OS: responders, 23.1 months vs. nonresponders, 8.0 months; hazard ratio [HR], 3.194; p < 0.001) and 4 months (median OS: responders, 26.5 months vs. nonresponders, 9.3 months; HR, 4.534; p < 0.001). Conclusion: Radiologic response assessed by mRECIST was a significant prognostic factor for OS in patients with advanced-stage HCC showing MVI treated with combined TACE plus RT. [ABSTRACT FROM AUTHOR]

Background: Repeated transarterial chemoembolization (TACE) can be associated with loss of its efficacy and subsequent tumor progression. Purpose: To identify features of gadoxetic acid-enhanced magnetic resonance imaging (MRI) associated with TACE refractoriness and to develop a prediction model for estimating the risk of TACE refractoriness. Material and Methods: Among 1025 patients with intermediate-stage hepatocellular carcinoma (HCC) who underwent TACE as a first-line treatment during 2010–2017, 427 patients who underwent preoperative gadoxetic acid-enhanced MRI were analyzed. According to the date of initial TACE, patients were divided into the development cohort (n = 211) and the test cohort (n = 216). TACE refractoriness was determined according to the Japan Society of Hepatology guidelines. Univariable and multivariable analyses were performed to investigate the association between clinical/MRI features and TACE refractoriness. The performance of the prediction model was internally and externally assessed using the C-index of discrimination and a Hosmer-Lemeshow goodness-of-fit test for calibration. Results: By analyzing 427 patients, we constructed a prediction model with the following independent features associated with TACE refractoriness: maximum tumor size; tumor number; peritumoral hypointensity on hepatobiliary phase (HBP); and the presence of non-hypervascular hypointense nodule on HBP. This system enabled the prediction of TACE refractoriness in the development cohort (C-index, 0.796) and the test cohort (C-index, 0.738) with good discrimination and calibration abilities. Conclusion: The prediction model based on gadoxetic acid-enhanced MRI features in addition to the known predictors including tumor size and number can be used to estimate the risk of TACE refractoriness in patients with intermediate-stage HCC. [ABSTRACT FROM AUTHOR]

Background and Aim: We compared the clinical outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) in small (≤ 3 cm) hepatocellular carcinoma. Methods: A total of 266 patients treated with RFA (n = 179) or SBRT (n = 87) were reviewed. Local control rates (LCRs), intrahepatic recurrence‐free survival (IHRFS) rates, and overall survival (OS) rates were compared. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline characteristics between the two groups. Results: The median follow‐up period was 50.3 months, and treatment method (RFA vs SBRT) was not a significant prognostic factor for LCR, OS, and IHRFS in both multivariate and IPTW‐adjusted analyses. The 4‐year LCRs after RFA and SBRT were 92.7% and 95.0%, respectively. Perivascular location was a significant prognostic factor for LCR in the entire patients and in the RFA group, but not in the SBRT group. The 4‐year OS rates in the RFA and SBRT groups were 78.1% and 64.1%, respectively (P = 0.012). After IPTW adjustment, the 4‐year LCRs (90.6% vs 96.3%) and OS rates (71.8% vs 70.2%) were not significantly different between the two groups. The rate of grade ≥ 3 adverse events was 0.6% (n = 1) in the RFA group and 1.1% (n = 1) in the SBRT group. Conclusions: The two treatment methods showed comparable outcomes in terms of LCR, OS rate, and IHRFS rate after IPTW adjustment. SBRT seems to be a viable alternative method for small hepatocellular carcinomas that are not suitable for RFA due to tumor location. [ABSTRACT FROM AUTHOR]

Background: Combined hepatocellular‐cholangiocarcinoma (cHCC‐CCA) can develop in patients with and without risk factors for hepatocellular carcinoma (HCC). Purpose: To compare the clinical and magnetic resonance imaging (MRI) characteristics of cHCC‐CCA in patients with and without risk factors for HCC, and to assess the influence of risk factors on patient prognosis. Study Type: Retrospective. Population: A total of 152 patients with surgically confirmed cHCC‐CCA. Field Strength/Sequence: 1.5‐T and 3‐T/T1‐weighted dual gradient‐echo in‐ and opposed‐phase, T2‐weighted turbo‐spin‐echo, diffusion‐weighted single‐shot spin‐echo echo‐planar, and T1‐weighted three‐dimensional gradient‐echo contrast‐enhanced sequences. Assessment: MRI features according to the Liver Imaging Reporting and Data System (LI‐RADS) and pathologic findings based on revised classification were compared between patients with and without risk factors for HCC. Overall survival (OS) and recurrence‐free survival (RFS) were also compared between the two groups, and factors associated with survival were evaluated. Statistical Tests: The clinico‐pathologic and MRI features of the two groups were compared using Student's t‐tests, Mann–Whitney U‐tests, and chi‐square tests. OS and RFS were evaluated by the Kaplan–Meier method, and factors associated with survival were evaluated by Cox proportional hazard model. Results: cHCC‐CCA in patients with risk factors were more frequently classified as LI‐RADS category 4 or 5 (LR‐4/5; probably or definitely HCC) (48.7%), whereas those without risk factors were more frequently classified as category M (LR‐M; probably malignant, not specific for HCC) (63.6%). RFS and OS did not differ significantly according to risk factors (P = 0.63 and 0.83). Multivariable analysis showed that pathologic tumor type (hazard ratio 2.02; P < 0.05) and LI‐RADS category (hazard ratio 2.19; P < 0.05) were significantly associated with RFS and OS, respectively. Data Conclusion: Although MRI features of cHCC‐CCA differed significantly between patients with and without risk factors for HCC, postsurgical prognosis did not. LI‐RADS category and pathologic tumor type were independently correlated with postsurgical prognosis in patients with cHCC‐CCA. Level of Evidence: 3 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: We compared surgical resection (SR) and radiofrequency ablation (RFA) as first-line treatment in patients with hepatocellular carcinoma (HCC) based on the risk of microvascular invasion (MVI). Background: The best curative treatment modality between SR and RFA in patients with HCC with MVI remains unclear. Methods: Data from 2 academic cancer center-based cohorts of patients with a single, small (≤3 cm) HCC who underwent SR were used to derive (n = 276) and validate (n = 101) prediction models for MVI using clinical and imaging variables. The MVI prediction model was developed using multivariable logistic regression analysis and externally validated. Early recurrence (<2 years) based on risk stratification between SR (n = 276) and RFA (n = 240) was evaluated via propensity score matching. Results: In the multivariable analysis, alpha-fetoprotein (≥15 ng/mL), protein induced by vitamin K absence-II (≥48 mAU/mL), arterial peritumoral enhancement, and hepatobiliary peritumoral hypointensity on magnetic resonance imaging were associated with MVI. Incorporating these factors, the area under the receiver operating characteristic curve of the predictive model was 0.87 (95% confidence interval: 0.82–0.92) and 0.82 (95% confidence interval: 0.74–0.90) in the derivation and validation cohorts, respectively. SR was associated with a lower rate of early recurrence than RFA based on the risk of MVI after propensity score matching (P < 0.05). Conclusions: Our model predicted the risk of MVI in patients with a small (≤ 3 cm) HCC with high accuracy. Patients with MVI who had undergone RFA were more vulnerable to recurrence than those who had undergone SR. [ABSTRACT FROM AUTHOR]

Background and Aim: The purpose of this study was to investigate the long‐term oncologic outcomes after stereotactic body radiation therapy (SBRT) for small hepatocellular carcinoma (HCC). Methods: A total of 290 patients with HCC were registered between March 2007 and July 2013. A dose of 10–15 Gy per fraction was given over three to four consecutive days, resulting in a total dose of 30–60 Gy. Overall and recurrence‐free survivals were estimated from the date of the start of SBRT to the date of death, the last follow‐up examination, or to the date of tumor recurrence. Results: The median follow‐up period of all patients was 38.2 months, and the median tumor size was 1.7 cm. Overall survival (OS) rate at 5 years was 44.9%. Multivariate analyses revealed that age, Child–Pugh class, tumor size, and albumin levels were significant factors for OS. The 5‐year local control rate was 91.3%. In multivariate analysis, tumor size and albumin were significantly associated with local tumor control. However, there was a negative correlation between total dose and tumor size in Pearson's correlation analysis (r = −0.111, P = 0.046). Conclusions: Stereotactic body radiation therapy was an excellent ablative treatment option for patients with small HCC. Tumor size was a significant factor for local tumor control after SBRT, although the total dose was negatively correlated with tumor size. Considering the low OS rates and the high local tumor control rates, the combined SBRT and systemic therapies may be beneficial for improving survival outcomes. [ABSTRACT FROM AUTHOR]

Controlling adverse events (AEs) through dose reduction can enhance drug adherence and treatment response. Currently, there is no guide for sorafenib dosing. The aim of this study was to evaluate whether sorafenib dosing could affect treatment outcomes. A total of 782 hepatocellular carcinoma (HCC) patients treated with sorafenib were evaluated for sorafenib dosing and its modifications via medical records at baseline and regular follow‐up. Study outcomes included progression‐free survival (PFS), overall survival (OS), sorafenib duration, cumulative dose, AEs and drug discontinuation. The median patient survival was 7.7 months. Overall, 242 (30.9%) patients underwent dose reduction and 121 (17.5%) discontinued sorafenib due to AEs. In multivariate analysis, dose reduction was identified to be independently predictive of PFS and OS. The 800‐to‐400 mg/day group provided significantly better PFS than the 800 mg/day‐maintained group or the 800‐to‐600 mg/day group. Likewise, the 800‐to‐400 mg/day group resulted in a significantly better OS than other dosing. However, dose reduction to 200 mg/day led to significantly worse PFS and OS. Hand‐foot skin reaction and drug discontinuation due to AEs were higher in the 800‐to‐600 mg/day group than the 800‐to‐400 mg/day group. The 800‐to‐400 mg/day group had significantly longer treatment duration and higher cumulative dose than the 800 mg/day‐maintained group. Sorafenib dose reduction can improve HCC survival and increase patient tolerance and adherence coupled with longer duration and higher cumulative dose. Dose reduction from 800 to 400 mg/day than to 600 mg/day is recommended when clinically warranted. However, dose reduction to 200 mg/day is not recommendable. What's new? Although sorafenib, a kinase inhibitor drug, is effective in the treatment of advanced liver cancer, a large fraction of patients discontinue treatment because of adverse events. Here the authors evaluated the effect of drug dosing on treatment outcome in a large cohort study in South Korea. They found that proper sorafenib dose reduction helped control adverse events, leading to increased patient adherence coupled with longer duration and ultimately improved patient survival. They propose that proper dose modifications are a key determinant of successful sorafenib treatment. [ABSTRACT FROM AUTHOR]

Background: Use of the Liver Imaging Reporting and Data System (LI-RADS) is increasing, but the reported results for interreader agreement seem quite variable.Purpose: To systematically determine the interreader agreement of LI-RADS on magnetic resonance imaging (MRI) and to determine the sources of heterogeneity between the reported results.Study Type: Systematic review and meta-analysis.Subjects: Fifteen original articles with 2968 lesions.Field Strength: 1.5T and 3.0T.Assessment: Two reviewers independently performed the data extraction. The reviewers identified and reviewed the original articles reporting the interreader agreement of LI-RADS using MRI.Statistical Tests: The meta-analytic pooled intraclass correlation coefficient (ICC) for lesion size and kappa value (κ) for major features (arterial-phase hyperenhancement [APHE], nonperipheral washout [WO], enhancing capsule [EC]) and LI-RADS categorization (LR) were calculated using the random-effects model. Sensitivity analysis and meta-regression analysis were performed to explore the cause of study heterogeneity.Results: The meta-analytic pooled ICC of lesion size was 0.97 (95% confidence interval [CI], 0.94-1.00). Meta-analytic pooled κ of APHE, WO, EC, and LR were 0.72 (95% CI, 0.62-0.82), 0.69 (95% CI, 0.60-0.78), 0.66 (95% CI, 0.58-0.74), and 0.70 (95% CI, 0.56-0.85), respectively. Substantial study heterogeneity was noted in all five variables (I2  ≥ 89.1%, P < 0.001). Study design, type, and clarity of blinding review were factors that significantly influenced study heterogeneity (P ≤ 0.05).Data Conclusion: LI-RADS demonstrated overall substantial interreader agreement for major features and the category on MRI, but showed heterogeneous results between studies.Level Of Evidence: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:795-804. [ABSTRACT FROM AUTHOR]

Background and Aims: The Liver Imaging Reporting and Data System (LI‐RADS) category M (LR‐M) was introduced to preserve the high specificity of LI‐RADS algorithm for diagnosing hepatocellular carcinoma (HCC). We aimed to systematically determine the probability of the LR‐M for HCC and non‐HCC malignancy, and to determine the sources of heterogeneity between reported results. Methods: Original studies reporting the probability of LR‐M for HCC and non‐HCC malignancy on magnetic resonance imaging (MRI) were identified in MEDLINE and EMBASE. The meta‐analytic pooled percentages of HCC and non‐HCC in LR‐M were calculated. Meta‐regression analysis was performed to explore study heterogeneity. The meta‐analytic frequency of each LR‐M imaging feature was determined. Results: We found 10 studies reporting the diagnostic performance of LR‐M (1819 lesions in 1631 patients), and six reporting the frequency of LR‐M imaging features. The pooled percentages of HCC and non‐HCC malignancy for LR‐M were 28.2% (95% confidence interval [CI], 23.8%‐33.1%; I2 = 83%) and 69.6% (95% CI, 64.6%‐74.1%; I2 = 83%) respectively. The study type and MRI scanner field strength were significantly associated with study heterogeneity (P ≤.04). Of the seven imaging features, rim arterial phase hyperenhancement showed the highest frequency in both non‐HCC (48.9%; 95% CI, 43.0%‐54.8%) and HCC groups (9.8%; 95% CI, 6.9%‐13.6%). Conclusions: The LR‐M category most commonly included non‐HCC malignancy but also included 28.2% of HCC. Substantial study heterogeneity was noted, and it was significantly associated with study type and MRI scanner field strength. In addition, the frequency of LR‐M imaging features was variable. [ABSTRACT FROM AUTHOR]

Background & aim: Hepatocellular carcinoma (HCC) is increasingly being detected at a very early‐stage due to the wide implementation of the surveillance of at‐risk patient populations combined with improved imaging technologies. Whether patients with HCC at a very early stage can be offered local ablation as a first‐line treatment option still remains controversial. We retrospectively compared the effectiveness of surgical resection (SR) and radiofrequency ablation (RFA) for Barcelona Clinic Liver Cancer (BCLC) very early‐stage HCC in patients with long‐term follow‐up. Methods: Propensity score analysis using inverse probability weighting (IPW) from a large‐volume liver centre. We included adult patients who between 2000 and 2013 received a diagnosis of very early‐stage HCC (BCLC stage 0; a single tumour ≤2 cm, Child‐Pugh A class, eastern cooperative oncology group [ECOG] 0) and who were treated with SR or RFA as the first‐line treatment. Results: We identified 1208 patients, 631 in the SR group and 577 in the RFA group. The median follow‐up time was 86.2 months. After propensity score analysis using IPW, the 15‐year overall survival rates were 60.4% and 51.6% in the SR and RFA group respectively. RFA group showed poorer overall survival than SR group (adjusted hazard ratio, 1.29; P = .0378). The 15‐year recurrence‐free survival rates were 37% and 23.6% in the SR and RFA group respectively (P < .001). Conclusion: For patients with very early‐stage HCC, the SR group was associated with better overall and recurrence‐free patient survival compared to the RFA group. Therefore, SR should be considered as the first‐line treatment for these patients. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy and safety of 144-week tenofovir disoproxil fumarate (TDF) therapy in treatment-naïve chronic hepatitis B (CHB) patients in Korean.Methods: In total, 579 treatment-naïve CHB patients at 11 medical centers were enrolled retrospective and prospective from September 2015 to January 2016 by design (NCT02533544). We evaluated the complete virologic response (CVR) rate and the renal safety of TDF.Results: The overall CVR rate was 69.4%, 87.0%, and 89.7% at weeks 48, 96, and 144, respectively. In the HBeAg-positive CHB patients, the CVR rate at weeks 48, 96, and 144 was 61.4%, 83.1%, and 89.6%, respectively. The rates of HBeAg loss and seroconversion at weeks 48, 96, and 144 were 16.6%, 23.5%, 34.1%, and 7.6%, 8.9%, 13.3%, respectively. In HBeAg-negative CHB patients, the CVR rate at weeks 48, 96, and 144 was 82.5%, 93.2%, and 90.0%, respectively. The rate of alanine aminotransferase normalization was 36.9%, 45.4%, and 46.8% at weeks 48, 96, and 144, respectively. Of the CHB patients, 0.9% showed an elevated creatinine (> 0.5 mg/dL from baseline). Age (≥ 60 years) was significantly associated with a decline in renal function at week 144 (P < 0.0001). Comorbidities (diabetes or hypertension) showed the tendency to reduce renal function (P = 0.0624). Hepatocellular carcinoma developed in 10 (1.7%) patients and was related to cirrhosis.Conclusions: TDF therapy induced sustained viral suppression and had a favorable safety profile over a 3-year period. However, close monitoring of renal function should be mandatory in treating CHB patients receiving TDF, particularly older patients. [ABSTRACT FROM AUTHOR]

Background: A real‐life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice. Methods: We analyzed 590 consecutively enrolled patients with CHC‐1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance‐associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen. Results: The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was "indeterminate." Overall, 518 patients were treated with a 24‐week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV‐"indeterminate" patients was not difference 95.0% in the RAV‐negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC. Conclusions: Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC‐1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate gadoxetic acid-enhanced magnetic resonance imaging (MRI) findings of combined hepatocellular cholangiocarcinoma (cHCC-CC) with special emphasis on correlation of MRI findings with histopathologic tumor characteristics and survival outcomes after curative surgery.Materials and Methods: Our Institutional Review Board approved this study, with a waiver of informed consent. For 82 patients (64 men, 18 women; mean age, 54.0 years; age range, 30-81) with surgically confirmed cHCC-CCs, we evaluated clinical features, histologic findings, and tumor morphologic and enhancement features on gadoxetic acid-enhanced liver MRI at 1.5T (n = 67) or 3.0T (n = 15). Imaging features of cHCC-CCs were correlated with pathologic findings according to the 2010 World Health Organization classification system. Tumors were categorized as hypervascular or nonhypervascular based on arterial phase enhancement and were compared with respect to overall and recurrence-free survival after curative-intent surgery.Results: Of the 82 lesions, 48 showing global arterial phase enhancement were categorized as the hypervascular group, while 34 lesions demonstrating rim, peripheral, or isoenhancement were categorized as the nonhypervascular group. There was no significant difference in MRI findings between pathologic tumor types (classical type versus stem cell feature type, P = 0.324-1.0). Compared with the nonhypervascular group, the hypervascular group had a larger HCC component (P = 0.014), smaller CC component (P = 0.001), and lesser amount of fibrotic stroma (P = 0.006) on pathologic analysis and was an independent factor associated with better overall survival after surgical resection (P = 0.033).Conclusion: Gadoxetic acid-enhanced MRI findings of cHCC-CCs were diverse, reflecting heterogeneous histologic features. The hypervascular group on MRI is associated with a larger HCC component, smaller CC component, less fibrotic stroma, and better overall survival after curative surgery than the nonhypervascular group.Level Of Evidence: 4 J. MAGN. RESON. IMAGING 2017;46:267-280. [ABSTRACT FROM AUTHOR]

Objective: Stereotactic body radiation therapy (SBRT) for the treatment of a malignancy in the liver requires the perilesional implantation of fiducial markers for lesion detection. The purpose of this study is to evaluate the efficacy and safety of ultrasound (US) -guided marker implantation for SBRT. Methods: We retrospectively reviewed 299, US–guided, intrahepatic fiducial markers implanted in 101 patients between November 2013 and September 2014. SBRT-planning CT images were analyzed to determine the technical success of the implantation, the mean distance between the tumor margin and the marker, with the ideal location of fiducials defined as the distance between a marker and a tumor less than 3 cm and the distance between markers greater than 2 cm according to the tumor conspicuity seen on gray-scale US and the artifact obscuring tumor margins. We also evaluated procedure-related major and minor complications. Results: Technical success was achieved in 291 (97.3%) fiducial marker implantations. The mean distance between the tumor and the marker was 3.1 cm (S.D., 2.1 cm; range, 0–9.5 cm). Of 101 patients, 72 lesions (71.3%, 2.2 ± 1.0 cm; range, 0–3.0 cm) had fiducial markers located in an ideal location. The ideal location of fiducials was more common in visible lesions than in poorly conspicuous lesions (90.2% vs. 52.0%, P < 0.001). Seventeen markers (5.8%) developed beam-hardening artifacts obscuring the tumor margins. There were no major complications, although 12 patients (11.9%) developed minor complications. Conclusions: US-guided implantation of fiducial markers in the liver is an effective and safe procedure with only rare complications. [ABSTRACT FROM AUTHOR]

Assigning a hepatocellular carcinoma (HCC) to an appropriate subtype is important because this guarantees the diagnosis and treatment and allows decisions regarding the prognosis of the patient. HCC subtyping is usually based on the World Health Organization (WHO) classification and the 2019 fifth edition is the latest version. However, the WHO classification system is still in evolution and has limited clinical relevance. We aimed to evaluate the clinical relevance of HCC subtyping and to reappraise some of the major subtypes of HCC. Our archived cases (n = 589) were reclassified according to the 2019 WHO system. The percentage of each subtype was mostly similar to that in the WHO classification. However, on the contrary to the 2019 WHO system, clear cell type HCC was associated with more frequent recurrence or metastasis. Meanwhile, macrotrabecular massive HCC was related to poor prognosis as demonstrated in the 2019 WHO system and should be described in the pathology report. For steatohepatitic HCC, there is a debate on whether it is a true subtype because the steatohepatitis morphology may or may not be present in the background liver. In our study, 44 % of steatohepatitic HCCs (n = 19/43) presented underlying steatohepatitis. Additionally, the background cirrhosis did not influence survival in the HCC patients, although the 2019 WHO system indicates the presence of cirrhosis as a poor prognostic factor. In conclusion, although it is not perfect yet, HCC subtyping based on the 2019 WHO system provides valuable information to manage patients with HCC. • Clinical relevance of HCC subtyping was clarified with the 2019 WHO classification. • Clear cell type HCC was associated with more frequent recurrence or metastasis than the NOS type. • Macrotrabecular massive HCC was related to poor prognosis and should be described in the pathology report. [ABSTRACT FROM AUTHOR]