Noninferiority Outcomes of Besifovir Compared to Tenofovir Alafenamide in Treatment-Naïve Patients with Chronic Hepatitis B.

Background/Aims: : Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB). However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB. Methods: : We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes. Results: : A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (-0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15. Conclusions: : BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.

Identification of patients with favorable prognosis after resection in intermediate-stage-hepatocellular carcinoma.

BACKGROUNDS: It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. METHODS: This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). RESULTS: A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median follow-up of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)=1.471, 95% CI: 1.199-1.803, P <0.001). On multivariate analysis, alpha-fetoprotein ≥5.0 ng/ml (aHR=0.202), ALBI grade ≥2 (aHR=0.709), tumor number ≥3 (aHR=0.404), and maximal tumor size ≥5 cm (aHR=0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR=5.834; validation: aHR=5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR=3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR=0.816). CONCLUSIONS: Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score.

Impact of Low Skeletal Muscle Mass on Long-Term Outcomes in Hepatocellular Carcinoma Treated with Trans-Arterial Radioembolization: A Retrospective Multi-Center Study.

Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90-loaded microspheres. This was a multi-center retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT), and 126 (36.3%) were classified as LSMM. The median overall survival (OS) was 28.1 months (95% CI, 24.8-35.7), and median progression-free survival was 8.0 months (95% CI, 6.4-9.4). Multivariate Cox regression analysis revealed that LSMM (hazard ratio [HR], 1.36; 95% CI, 1.00-1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33-2.49, p < 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04-1.92, p = 0.03), and albumin-bilirubin grade (2-3) (HR 1.74; 95% CI, 1.24-2.43, p < 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment LSMM independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.

A machine learning model for predicting hepatocellular carcinoma risk in patients with chronic hepatitis B.

BACKGROUND: Machine learning (ML) algorithms can be used to overcome the prognostic performance limitations of conventional hepatocellular carcinoma (HCC) risk models. We established and validated an ML-based HCC predictive model optimized for patients with chronic hepatitis B (CHB) infections receiving antiviral therapy (AVT). METHODS: Treatment-naïve CHB patients who were started entecavir (ETV) or tenofovir disoproxil fumarate (TDF) were enrolled. We used a training cohort (n = 960) to develop a novel ML model that predicted HCC development within 5 years and validated the model using an independent external cohort (n = 1937). ML algorithms consider all potential interactions and do not use predefined hypotheses. RESULTS: The mean age of the patients in the training cohort was 48 years, and most patients (68.9%) were men. During the median 59.3 (interquartile range 45.8-72.3) months of follow-up, 69 (7.2%) patients developed HCC. Our ML-based HCC risk prediction model had an area under the receiver-operating characteristic curve (AUC) of 0.900, which was better than the AUCs of CAMD (0.778) and REAL B (0.772) (both p < .05). The better performance of our model was maintained (AUC = 0.872 vs. 0.788 for CAMD and 0.801 for REAL B) in the validation cohort. Using cut-off probabilities of 0.3 and 0.5, the cumulative incidence of HCC development differed significantly among the three risk groups (p < .001). CONCLUSIONS: Our new ML model performed better than models in terms of predicting the risk of HCC development in CHB patients receiving AVT.

Inverse Propensity Score-Weighted Analysis of Entecavir and Tenofovir Disoproxil Fumarate in Patients with Chronic Hepatitis B: A Large-Scale Multicenter Study.

Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) in preventing hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients; however, it remains controversial. This study aimed to conduct comprehensive comparisons between the two antivirals. CHB patients initially treated with ETV or TDF between 2012 and 2015 at 20 referral centers in Korea were included. The primary outcome was the cumulative incidence of HCC. The secondary outcomes included death or liver transplantation, liver-related outcome, extrahepatic malignancy, development of cirrhosis, decompensation events, complete virologic response (CVR), seroconversion rate, and safety. Baseline characteristics were balanced using the inverse probability of treatment weighting (IPTW). Overall, 4210 patients were enrolled: 1019 received ETV and 3191 received TDF. During the median follow-ups of 5.6 and 5.5 years, 86 and 232 cases of HCC were confirmed in the ETV and TDF groups, respectively. There was no difference in HCC incidence between the groups both before (p = 0.36) and after IPTW was applied (p = 0.81). Although the incidence of extrahepatic malignancy was significantly higher in the ETV group than in the TDF group before weighting (p = 0.02), no difference was confirmed after IPTW (p = 0.29). The cumulative incidence rates of death or liver transplantation, liver-related outcome, new cirrhosis development, and decompensation events were also comparable in the crude population (p = 0.24-0.91) and in the IPTW-adjusted population (p = 0.39-0.80). Both groups exhibited similar rates of CVR (ETV vs. TDF: 95.1% vs. 95.8%, p = 0.38), and negative conversion of hepatitis B e antigen (41.6% vs. 37.2%, p = 0.09) or surface antigen (2.8% vs. 1.9%, p = 0.10). Compared to the ETV group, more patients in the TDF group changed initial antivirals due to side effects, including decreased kidney function (n = 17), hypophosphatemia (n = 20), and osteoporosis (n = 18). In this large-scale multicenter study, ETV and TDF demonstrated comparable effectiveness across a broad range of outcomes in patients with treatment-naïve CHB during similar follow-up periods.

Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study.

Background/Aim: Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. Methods: This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. Results: In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. Conclusions: This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis.

BACKGROUND/AIMS: Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. METHODS: This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). RESULTS: In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28-0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0-56.7%, whereas that of the TKI group was 12.3-15.0%. CONCLUSION: For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.

CAGE-B and SAGE-B models better predict the hepatitis B virus-related hepatocellular carcinoma after 5-year entecavir treatment than PAGE-B.

OBJECTIVES: The PAGE-B model consists of variables at the initiation of antiviral therapy (AVT), whereas the SAGE-B and CAGE-B models consist of variables after 5 years of AVT. We aimed to compare the predictive accuracy of three risk prediction models for hepatocellular carcinoma (HCC) development after 5 years of AVT in patients with chronic hepatitis B (CHB). METHODS: A total of 1335 patients who initiated entecavir (ETV) treatment between 2006 and 2011 and were followed up for more than 5 years were enrolled in the study. RESULTS: At ETV initiation, the median age was 49 years and the median score of the PAGE-B model was 14. After 5 years of ETV treatment, the median SAGE-B and CAGE-B scores were 6 and 6. During the study period, 93 (7.0%) patients developed HCC after 5-year treatment. In multivariate analysis, PAGE-B (hazard ratio [HR] 1.151, 95% confidence interval [CI] 1.087-1.219), SAGE-B (HR 1.340, 95% CI 1.228-1.463), and CAGE-B (HR 1.327, 95% CI 1.223-1.440) models independently predicted HCC development after 5 years of treatment (all P < 0.001). The high-risk groups of the three risk prediction models showed a significantly higher risk of HCC development compared to the medium- and low-risk groups (both P < 0.05). The AUROC of the SAGE-B (0.772-0.844) and CAGE-B (0.785-0.838) models was significantly higher than those of the PAGE-B model (0.696-0.745) in predicting HCC development after 5 years of treatment (both P < 0.05). CONCLUSION: The SAGE-B and CAGE-B models might be better than the PAGE-B model in predicting HCC development after 5 years of ETV treatment.

Personalized Antiviral Drug Selection in Patients With Chronic Hepatitis B Using a Machine Learning Model: A Multinational Study.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) for the prevention of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B; however, it has distinct long-term renal and bone toxicities. This study aimed to develop and validate a machine learning model (designated as Prediction of Liver cancer using Artificial intelligence-driven model for Network-antiviral Selection for hepatitis B [PLAN-S]) to predict an individualized risk of HCC during ETV or TDF therapy. METHODS: This multinational study included 13,970 patients with chronic hepatitis B. The derivation (n = 6,790), Korean validation (n = 4,543), and Hong Kong-Taiwan validation cohorts (n = 2,637) were established. Patients were classified as the TDF-superior group when a PLAN-S-predicted HCC risk under ETV treatment is greater than under TDF treatment, and the others were defined as the TDF-nonsuperior group. RESULTS: The PLAN-S model was derived using 8 variables and generated a c-index between 0.67 and 0.78 for each cohort. The TDF-superior group included a higher proportion of male patients and patients with cirrhosis than the TDF-nonsuperior group. In the derivation, Korean validation, and Hong Kong-Taiwan validation cohorts, 65.3%, 63.5%, and 76.4% of patients were classified as the TDF-superior group, respectively. In the TDF-superior group of each cohort, TDF was associated with a significantly lower risk of HCC than ETV (hazard ratio = 0.60-0.73, all P < 0.05). In the TDF-nonsuperior group, however, there was no significant difference between the 2 drugs (hazard ratio = 1.16-1.29, all P > 0.1). DISCUSSION: Considering the individual HCC risk predicted by PLAN-S and the potential TDF-related toxicities, TDF and ETV treatment may be recommended for the TDF-superior and TDF-nonsuperior groups, respectively.

Comparable outcomes between immune-tolerant and active phases in noncirrhotic chronic hepatitis B: a meta-analysis.

BACKGROUND: Antiviral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant (IT) phase. We compared the outcomes between the untreated IT phase and the treated immune-active (IA) phase in noncirrhotic HBeAg-positive CHB patients. METHODS: We systematically searched 4 databases, including PubMed, Medline, Embase, and Cochrane, until August 2021. The pooled incidence rates of HCC and mortality in the IT and IA cohorts and phase change in the IT cohort were investigated. Studies that included patients with liver cirrhosis were excluded. RESULTS: Thirteen studies involving 11,903 patients were included. The overall median of the median follow-up period was 62.4 months. The pooled 5-year and 10-year incidence rates of HCC were statistically similar between the IT and IA cohorts (1.1%, 95% CI: 0.4%-2.8% vs. 1.1%, 95% CI: 0.5%-2.3%, and 2.7%, 95% CI: 1.0%-7.3% vs. 3.6%, 95% CI: 2.4%-5.5%, respectively, all p>0.05). The pooled 5-year odds ratio of HCC between IT and IA cohorts was 1.05 (95% CI: 0.32-3.45; p=0.941). The pooled 5-year incidence rate of mortality was statistically similar between the IT and IA cohorts (1.9%, 95% CI: 1.1%-3.4% vs. 1.0%, 95% CI: 0.3%-2.9%, p=0.285). Finally, the pooled 5-year incidence rate of phase change in the IT cohort was 36.1% (95% CI: 29.5%-43.2%). CONCLUSION: The pooled incidence rates of HCC and mortality were comparable between the untreated IT and the treated IA phases in noncirrhotic HBeAg-positive CHB patients.

The clinical effect of antiviral therapy in patients with hepatitis B virus-related decompensated cirrhosis and undetectable DNA.

BACKGROUND AND AIM: Antiviral therapy (AVT) is the mainstay of hepatitis B virus (HBV) management. We investigated whether AVT improves the outcomes of HBV-related decompensated cirrhosis and undetectable HBV-DNA. METHODS: Between 2000 and 2017, treatment-naïve patients with HBV-related decompensated cirrhosis and undetectable HBV-DNA were recruited from two tertiary hospitals. The endpoints included death and hepatocellular carcinoma (HCC). RESULTS: A total of 429 patients were analyzed (50 and 379 patients in the AVT and non-AVT groups, respectively). Patients in the AVT group were significantly younger and had higher alanine aminotransferase and alpha-fetoprotein levels than those in the non-AVT group (all P < 0.05). During follow-up (median 49.6 months), 98 patients died and 105 developed HCC. The cumulative incidence rates of death (2.0%, 4.1%, and 6.4%, and 4.9%, 7.2%, and 10.2% at 6 months, 1 year, and 2 years, respectively) and HCC (8.6%, 15.8%, and 26.4% vs 1.6%, 7.7%, and 24.4% at 1, 2, and 5 years, respectively) were statistically comparable between the AVT and non-AVT groups (all P > 0.05). Using Cox regression analysis, AVT was not significantly associated with death nor HCC (all P > 0.05). Similar results were observed after balancing baseline characteristics with inverse probability of treatment weighting. In the non-AVT group, the cumulative incidence rates of HBV-DNA detection at 6 months, 1 year, and 2 years were 2.0%, 3.1%, and 6.4%, respectively. CONCLUSIONS: Antiviral therapy did not attenuate the risk of death nor HCC in patients with HBV-related decompensated cirrhosis and undetectable HBV-DNA.

Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune-tolerant phase.

BACKGROUND/AIMS: The histologic status of the immune-tolerant (IT) phase of chronic hepatitis B relative to long-term outcomes is unclear. This study aimed to discover how the serological criteria currently in use correspond to histologic criteria in determining the IT phase and indication for liver biopsy. METHODS: Patients in the serological IT phase determined by positive hepatitis B e antigen, hepatitis B virus (HBV) DNA ≥106 IU/mL, and normal or minimally elevated alanine aminotransferase (ALT) ≤60 IU/L, who underwent liver biopsy at three different hospitals were included. The distribution of the histologic IT phase, defined as fibrosis of stage 1 or less and inflammation of grade 1 or less, was compared with that of the serological IT phase. The risk factors for the incidence of liver-related events, such as hepatocellular carcinoma, liver cirrhosis, liver transplantation, and death, were also analyzed. RESULTS: Eighty-two (31.7%) out of 259 clinically suspected IT phase patients belonged to the histologic IT phase. Age over 35, high AST, and low albumin were useful for ruling out the histologic IT phase. Risk factors predicting liver-related events were age and significant fibrosis stage. There was no significant difference in the proportion of histologic IT phase and clinical prognosis between normal ALT and mildly elevated ALT groups. However, even in patients with normal ALT, age was an important factor in predicting the presence of the histologic IT phase. CONCLUSION: A significant number of patients who belonged to the serological IT phase were not in the histologic IT phase. Patients over 35 years and those with high AST, low albumin, and low HBV DNA levels were more likely to experience poor long-term clinical outcomes. Therefore, additional histologic assessment should be considered.

Long-Term Prediction Model for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Antiviral Therapy: Based on Data from Korean Patients.

Predicting the development of hepatocellular carcinoma (HCC) is a key clinical issue in patients with chronic hepatitis B (CHB). The aim of this study was to develop a precise and simple HCC risk score for up to 10 years. A total of 1895 CHB patients treated with entecavir or tenofovir disoproxil fumarate were retrospectively recruited and randomized into derivation (n = 1239) and validation cohorts (n = 656). Variables proven to be independent risk factors for HCC in the derivation cohort were used to develop the prediction model. The ACCESS-HCC model included five variables (age, cirrhosis, consumption of ethanol, liver stiffness, and serum alanine aminotransferase). Areas under curves were 0.798, 0.762, and 0.883 for HCC risk at 3, 5, and 10 years, respectively, which were higher than those of other prediction models. The scores were categorized according to significantly different HCC incidences: 0-4, low; 5-8, intermediate; and 9-14, high-risk. The annual incidence rates were 0.5%, 3.2%, and 11.3%, respectively. The performance of this model was validated in an independent cohort. The ACCESS-HCC model shows improved long-term prediction and provides three distinct risk categories for HCC in CHB patients receiving antiviral therapy. Further research is needed for external validation using larger cohorts.

Impacts of muscle mass dynamics on prognosis of outpatients with cirrhosis.

BACKGROUND/AIMS: Sarcopenia negatively affects the prognosis of cirrhotic patients, but clinical implications of changes in muscle mass remain unclear. We aimed to elucidate its role in the prognosis of outpatients with cirrhosis. METHODS: Patients with cirrhosis who underwent annual abdominal computed tomography (CT) for hepatocellular carcinoma surveillance were included in the prospective cohort. The L3 skeletal muscle index (SMI) was adopted as a proxy for the amount of skeletal muscle, and the rate of SMI change between inclusion and after 1 year (ΔSMI/yr%) was calculated. RESULTS: In total, 595 patients underwent a second CT after 1 year. Among them, 109 and 64 patients had sarcopenia and Child-Pugh class B/C decompensation at inclusion, which changed to 103 and 45 at the 1-year follow-up, respectively. During a median follow-up of 30.1 months after 1 year, 86 patients had at least one cirrhosis complication, and 18 died or received liver transplantation. In the development of cirrhosis complications, ΔSMI/yr% was independently associated, even after adjusting for the Child-Pugh and model for end stage liver disease (MELD)-Na scores. In addition, ΔSMI/yr% showed a good predictive performance for the development of cirrhosis complications within 6 months after 1-year follow-up in all subgroups, with a cut-off of -2.62 (sensitivity, 83.9%; specificity, 74.5%) in the overall population. SMI at 1-year and Child-Pugh score were independent factors associated with survival. In addition, changes in sarcopenia status significantly stratified survival. CONCLUSION: ΔSMI/yr% was a good predictor of the development of cirrhosis complications in outpatients with cirrhosis, independent of Child-Pugh and MELD scores.

Magnetic resonance imaging improves stratification of fibrosis and steatosis in patients with chronic liver disease.

PURPOSE: We aimed to compare the diagnostic accuracy of magnetic resonance imaging (MRI) and transient elastography (TE) in assessing liver fibrosis and steatosis in patients with chronic liver disease (CLD). METHODS: Patients who underwent liver biopsy or liver surgery at two academic hospitals between 2017 and 2021 were retrospectively recruited. The stages of liver fibrosis and steatosis were evaluated using histologic examination. Liver stiffness (LS) was assessed using MR elastography (LSMRE) and TE (LSTE). Liver steatosis was assessed using proton density fat fraction (PDFF) and controlled attenuation parameter (CAP). RESULTS: The mean age of the study population (n = 280) was 53.6 years and male sex predominated (n = 199, 71.1%). Nonalcoholic fatty liver disease was the most prevalent (n = 127, 45.5%), followed by hepatitis B virus (n = 112, 40.0%). Hepatocellular carcinoma was identified in 130 patients (46.4%). The proportions of F0, F1, F2, F3, and F4 fibrosis were 13.2%, 31.1%, 9.6%, 16.4%, and 29.7%, respectively. LSMRE had a significantly greater AUROC value than LSTE for detecting F2-F4 (0.846 vs. 0.781, P = 0.046), whereas LSMRE and LSTE similarly predicted F1-4, F3-4, and F4 (all P > 0.05). The proportions of S0, S1, S2, and S3 steatosis were 34.7%, 49.6%, 12.5%, and 3.2%, respectively. PDFF had significantly greater AUROC values than CAP in predicting S1-3 (0.922 vs. 0.806, P < 0.001) and S2-3 (0.924 vs. 0.795, P = 0.005); however, PDFF and CAP similarly predicted S3 (P = 0.086). CONCLUSION: MRI exhibited significantly higher diagnostic accuracy than TE for detecting significant fibrosis and mild or moderate steatosis in patients with CLD.

Efficacy and feasibility of surgery and external radiotherapy for hepatocellular carcinoma with portal invasion: A meta-analysis.

BACKGROUND: External beam radiation therapy (EBRT) and surgery are local treatment modalities for patients with hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). This meta-analysis aims to evaluate the effectiveness and feasibility of these treatment modalities. METHODS: PubMed, Medline, Embase, and Cochrane Library databases were systematically searched until April 2021. The primary endpoint was overall survival (OS) of the patients; the adverse effects of the treatment were also investigated. RESULTS: A total of 59 studies involving 9525 patients with HCC and PVT were included in this meta-analysis. All studies were non-randomized series, including seven comparative studies, and the remainder were single-arm studies or studies with comparative groups other than surgery or EBRT. The pooled rates of Child-Pugh class A were 74.6% and 95.3% in the EBRT and surgery arms, respectively, and the pooled main PVT rates were 40.7% and 15.5% in the EBRT and surgery arms, respectively (p < 0.001). Pooled 1- and 2-year OS rates of the EBRT arm were 44.1% (95% CI:40.3-48.0) and 21.7% (95% CI:18.9-24.8), respectively. In the subgroup of EBRT studies without main PVT, pooled 1- and 2-year OS rates were 59.9% (95% CI:48.9-70.1) and 30.5% (95% CI:15.2-51.8), respectively. In the surgery arm, the correlation rates were 62.8% (95% CI:55.0-70.0) and 42.5% (95% CI:34.4-51.0), respectively. The pooled 1-, and 2-year OS rates of surgery arm were significantly higher than those of EBRT arm (ps < 0.001), and not significantly different with the EBRT subgroup without main PVT (p = 0.762, 0.353, respectively). In studies of surgery accompanied by EBRT, the 1- and 2-year OS rates were 77.1% (95% CI:69.6-83.2) and 45.4% (95% CI:19.8-73.7), respectively. The pooled rates of grade≥3 toxicities ranged from 1.8 to 4.3%, depending on the type. CONCLUSION: Surgery can yield a favorable survival outcome, whereas EBRT can be widely considered for patients, including those with inferior clinical profiles. Further studies are warranted to determine the possibility of improving the clinical outcomes of surgery accompanied by EBRT.

Hepatitis B Core-Related Antigen Is Useful for Predicting Phase and Prognosis of Hepatitis B e Antigen-Positive Patients.

The role of hepatitis B core-related antigen (HBcrAg) level in defining clinical phase and predicting prognosis of chronic hepatitis B (CHB) has not been fully studied. CHB patients who had undergone liver biopsy in Korea University Medical Center were included. Patients with liver cirrhosis were excluded. The associations of HBcrAg level with CHB phase, and nucleos(t)ide analogue (NA)-induced hepatitis B e antigen (HBeAg) seroconversion were analyzed. In total, 387 patients (median follow-up of 82.4 months) were included. The CHB phases of patients were defined histologically as immune-tolerant (IT, n = 32, 8.3%), HBeAg-positive and immune-active (PIA, n = 211, 54.5%), HBeAg-negative and immune-active (n = 125, 32.3%), and inactive (n = 19, 4.9%), respectively. In HBeAg-positive patients, the mean HBV DNA levels were comparable between the two groups (p = 0.990). However, the mean HBsAg (7.4 log IU/mL and 6.9 log IU/mL, p = 0.002) and HBcrAg levels (8.2 log U/mL vs. 7.6 log U/mL, p < 0.001) of IT patients were significantly higher than that of PIA patients. In multivariate analysis, younger age (odds ratio [OR] 0.949, p = 0.025), lower alanine aminotransferase (OR 0.988, p = 0.002) and higher HBcrAg level (OR = 2.745 p = 0.022) were independent predictors of the IT phase. Of the patients in the PIA phase, 194 received NA after liver biopsy, and 61 (31.4%) had achieved HBeAg seroconversion after antiviral therapy. In Cox regression analysis, the higher HBcrAg level was the only independent predictor of the NA-induced HBeAg seroconversion (hazard ratio 1.285, p = 0.028). The HBcrAg level is useful for predicting clinical phase of CHB and NA-induced HBeAg seroconversion in HBeAg-positive patients.

Transarterial Radioembolization for Unresectable Hepatocellular Carcinoma: Real-Life Efficacy and Safety Analysis of Korean Patients.

Transarterial radioembolization (TARE) has become widely used in the treatment of HCC, one of the most common causes of cancer mortality worldwide. Here we investigated the long-term clinical outcomes of patients with hepatocellular carcinoma (HCC) treated with TARE in a multi-medical center in Korea. A total of 149 patients treated with TARE from 2008-2014 were recruited. The pre-treatment HCC stage was classified according to the BCLC stage, of which C and D were defined as advanced HCC. Advanced HCC stage and Child-Turcotte-Pugh (CTP) score A were identified in 62 (42%) and 134 (90%) patients, respectively. Portal vein thrombosis (PVT) was identified in 58 patients (38.9%). The median time to progression (TTP) was 14 months, and the median overall survival (OS) and progression-free survival (PFS) were 18.6 and 8.9 months, respectively. The overall tumor response was 47%, and the disease control rate was 78%. OS and PFS differed significantly according to the presence of liver cirrhosis, extrahepatic metastasis, tumor response and curative treatment after TARE (all, p < 0.05). Multiple tumors and major PVT were other independent factors related to OS, while the des-gamma carboxy protein level predicted PFS (all, p < 0.05). Tumor size was an independent predictor of tumor response. TTP, OS and PFS all differed among BCLC stages. The serious adverse effect after TARE was clinically not significant. Therefore, TARE is safe and effective in treating early to advanced HCCs.

Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B.

BACKGROUND & AIMS: Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC. METHODS: The incidence of HCC was evaluated in Korean patients with chronic hepatitis B who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort. RESULTS: A total of 9143 Korean patients (mean age, 49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median, 5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.26-0.66), propensity score-matching (aHR, 0.46; 95% CI, 0.28-0.76), and inverse probability weighting analyses (aHR, 0.44; 95% CI, 0.28-0.70). In the Caucasian cohort (n = 719; mean age, 51.8 years; HBeAg-positive, 20.3%; cirrhosis, 34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR, 0.21; 95% CI, 0.00-1.67). CONCLUSIONS: This multinational cohort study implies that HBeAg positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.