Clinical and Radiologic Predictors of Response to Atezolizumab-Bevacizumab in Advanced Hepatocellular Carcinoma.

Purpose: This study aimed to identify clinical and radiologic characteristics that could predict response to atezolizumab-bevacizumab combination therapy in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: This single-center retrospective study included 108 advanced HCC patients with intrahepatic lesions who were treated with atezolizumab-bevacizumab. Two radiologists independently analyzed Imaging characteristics of the index tumor on pretreatment computed tomography. Predictive factors associated with progressive disease (PD) at the best response based on Response Evaluation Criteria in Solid Tumors, Version 1.1 were evaluated using logistic regression analysis. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared with the log-rank test. Results: Of 108 patients with a median PFS of 15 weeks, 40 (37.0%) had PD during treatment. Factors associated with PD included the presence of extrahepatic metastases (adjusted odds ratio [aOR], 4.13; 95% confidence interval [CI], 1.19-14.35; p=0.03), the infiltrative appearance of the tumor (aOR, 3.07; 95% CI, 1.05-8.93; p=0.04), and the absence of arterial phase hyperenhancement (APHE) (aOR, 6.34; 95% CI, 2.18-18.47; p<0.001). Patients with two or more of these factors had a PD of 66.7% and a median PFS of 8 weeks, indicating a significantly worse outcome compared to the patients with one or no of these factors. Conclusion: In patients with advanced HCC treated with atezolizumab-bevacizumab treatment, the absence of APHE, infiltrative appearance of the intrahepatic tumor, and presence of extrahepatic metastases were associated with poor response and survival. Evaluation of early response may be necessary in patients with these factors.

Dynamic liver volume change in predicting hepatic decompensation and long-term effects of stereotactic body radiation therapy.

BACKGROUND AND AIM: This study aimed to investigate the association between liver volume change and hepatic decompensation and compare the risk of hepatic decompensation in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) who underwent stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of SBRT-treated HCC and compensated LC without HCC patients was conducted. Liver volume was measured using auto-segmentation software on liver dynamic computed tomography scans. The decompensation event was defined as the first occurrence of refractory ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. We evaluated the association between the rate of liver volume decrease and hepatic decompensation and compared decompensation events between the SBRT and LC cohorts using propensity score matching. RESULTS: A total of 138 patients from the SBRT cohort and 488 from the LC cohort were analyzed. The rate of liver volume decrease was associated with the risk of decompensation events in both cohorts. The 3-year rate of decompensation events was significantly higher in the group with a liver volume decreasing rate > 7%/year compared with the group with a rate < 7%/year. In the propensity score-matched cohort, the 3-year rate of decompensation events after a single session of SBRT was not significantly different from that in the LC cohort. CONCLUSIONS: The rate of liver volume decrease was significantly associated with the risk of hepatic decompensation in both HCC patients who received SBRT and LC patients. A single session of SBRT for HCC did not result in a higher decompensation rate compared with LC.

Outcomes of Liver Resection and Transarterial Chemoembolization in Patients with Multinodular BCLC-A Hepatocellular Carcinoma.

Background: This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation. Methods: We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups. Results: Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (p <0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS <0.05). Conclusion: In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.

The associations between fibrosis changes and liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: The prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with liver fibrosis. We investigated the associations between changes in liver stiffness measurement (LSM) over 3-year period and the development of cirrhosis or hepatocellular carcinoma (HCC) in patients with MASLD. METHODS: This study involved patients with MASLD who underwent transient elastography at baseline and 3 years after baseline from 2012 to 2020. Low (L), indeterminate (I) and high (H) LSM values were classified as <8 kPa, 8-12 kPa and >12 kPa respectively. RESULTS: Among 1738 patients, 150 (8.6%) were diagnosed with cirrhosis or HCC. The proportions of patients with L, I and H risk were 69.7%, 19.9% and 10.5% at baseline, and 78.8%, 12.8% and 8.4% at 3 years after baseline, respectively. The incidence rates of cirrhosis or HCC per 1000 person-years were 3.7 (95% confidence interval [CI], 2.4-5.5) in the L → L + I group, 23.9 (95% CI, 17.1-32.6) in the I → L + I group, 38.3 (95% CI, 22.3-61.3) in the H → L + I group, 62.5 (95% CI, 32.3-109.2) in the I → H group, 67.8 (95% CI, 18.5-173.6) in the L → H group and 93.9 (95% CI 70.1-123.1) in the H → H group. Two risk factors for the development of cirrhosis or HCC were LSM changes and low platelet counts. CONCLUSION: LSM changes could predict clinical outcomes in patients with MASLD. Thus, it is important to monitor changes in the fibrotic burden by regular assessment of LSM values.

CAMP-B score predicts the risk of hepatocellular carcinoma in patients with chronic hepatitis B after HBsAg seroclearance.

BACKGROUND: Risk of hepatocellular carcinoma (HCC) persists after hepatitis B surface antigen (HBsAg) seroclearance in patients with chronic hepatitis B (CHB). AIMS: To identify risk factors and construct a predictive model for HCC development. METHODS: We retrospectively analysed patients with CHB with HBsAg seroclearance. Primary outcome was HCC development. Factors identified from a multivariate Cox model in the training cohort, consisting of 3476 patients from two Korean hospitals, were used to construct the prediction model. External validation was performed using data from 5255 patients in Hong Kong. RESULTS: In the training cohort, HCC occurred in 102 patients during 24,019 person-years of observation (0.43%/year). Risk scores were assigned to cirrhosis (C:3), age ≥50 years (A:2), male sex (M:3) and platelet count <150,000/mm3 (P:1); all were independently associated with an increased risk of HCC in multivariate analysis The time-dependent area under receiver operating characteristic curves for 5, 10 and 15 years in the training and validation cohorts were 0.782, 0.817 and 0.825 and 0.785, 0.771 and 0.796, respectively. In the validation cohort, 85 patients developed HCC (0.24%/year). The corresponding incidence of HCC in the low-, intermediate- and high-risk groups were 0.07%, 0.37% and 0.90%, respectively. CONCLUSIONS: The CAMP-B score (cirrhosis, age ≥50 years, male sex and platelet count <150,000/mm3/L) was significantly associated with HCC development after HBsAg seroclearance. CAMP-B score can be easily implemented in real-world clinical practice and helps stratify HCC risk in patients with CHB following HBsAg seroclearance.

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.

Response to atezolizumab plus bevacizumab specific for lung and lymph node metastases affects survival of patients with HCC.

BACKGROUND & AIMS: Tumour microenvironment heterogeneity among different organs can influence immunotherapy responses. Here, we evaluated the impact of differential organ-specific responses on survival in patients with advanced-stage hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atezo/Bev). METHODS: We retrospectively analysed 366 consecutive patients with advanced-stage HCC treated with Atezo/Bev as first-line systemic treatment. Therapeutic response was assessed using RECIST v1.1. Patients were divided into an intention-to-treat (ITT) group (patients treated with ≥1 dose of Atezo/Bev) and a per-protocol (PP) analysis group (patients with at least one measurable lesion irrespective of location treated with ≥3 doses of Atezo/Bev). Overall response and organ-specific response at initial and best response were evaluated in the PP group. Responders were defined as patients achieving complete remission or partial response. Initial progressors were defined as patients with progressive disease after three doses of Atezo/Bev. RESULTS: The ITT and PP groups comprised 324 and 236 patients, respectively. In the PP group, the organ-specific response rate of lung and lymph node (LN) metastases at both initial and best responses were higher than those of intrahepatic lesions and macrovascular tumour thrombosis. Lung and LN-specific response rates were 21.1% and 23.5%, respectively, at initial response, and 24.7% and 31.4%, respectively, at best response. Both initial pulmonary and lymphatic progressors (adjusted hazard ratios [95% confidence intervals], 6.37 [2.10-19.3], and 8.36 [2.16-32.4], respectively) were independently associated with survival regardless of intrahepatic response. CONCLUSIONS: The response of metastatic HCC to the Atezo/Bev regimen may be used to determine whether to continue treatment or switch to second-line treatment at an early phase of therapy.

Prediction of Hepatocellular Carcinoma Development in Korean Patients after Hepatitis C Cure with Direct-Acting Antivirals.

Background/Aims: With the wide application of direct-acting antivirals (DAAs) for hepatitis C virus infection, the number of patients achieving a sustained virologic response (SVR) will continue to increase. However, no consensus has been achieved on exempting SVR-achieving patients from hepatocellular carcinoma (HCC) surveillance. Methods: Between 2013 and 2021, 873 Korean patients who achieved SVR following DAA treatment were analyzed. We evaluated the predictive performance of seven noninvasive scores (PAGE-B, modified PAGE-B, Toronto HCC risk index, fibrosis-4, aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin, and age male albumin-bilirubin platelet [aMAP]) at baseline and after SVR. Results: The mean age of the 873 patients (39.3% males) was 59.1 years, and 224 patients (25.7%) had cirrhosis. During 3,542 person-years of follow-up, 44 patients developed HCC, with an annual incidence of 1.24/100 person-years. Male sex (adjusted hazard ratio [AHR], 2.21), cirrhosis (AHR, 7.93), and older age (AHR, 1.05) were associated with a significantly higher HCC risk in multivariate analysis. The performance of all scores at the time of SVR were numerically better than those at baseline as determined by the integrated area under the curve. Time-dependent area under the curves for predicting the 3-, 5-, and 7-year risk of HCC after SVR were higher in mPAGE-B (0.778, 0.746, and 0.812, respectively) and aMAP (0.776, 0.747, and 0.790, respectively) systems than others. No patients predicted as low-risk by the aMAP or mPAGE-B systems developed HCC. Conclusions: aMAP and mPAGE-B scores demonstrated the highest predictive performance for de novo HCC in DAA-treated, SVR-achieving patients. Hence, these two systems may be used to identify low-risk patients that can be exempted from HCC surveillance.

Non-linear association of baseline viral load with on-treatment hepatocellular carcinoma risk in chronic hepatitis B.

OBJECTIVE: The association between baseline pretreatment serum HBV DNA levels and on-treatment hepatocellular carcinoma (HCC) risk remains controversial in patients with chronic hepatitis B (CHB). We aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in CHB patients without cirrhosis. DESIGN: Using a multicentre historical cohort study including 4693 hepatitis B e antigen (HBeAg)-negative and HBeAg-positive, adult CHB patients without cirrhosis who initiated antiviral treatment, HCC risk was estimated by baseline HBV viral load as a categorical variable. RESULTS: During a median of 7.6 years of antiviral treatment, 193 patients developed HCC (0.53 per 100 person- years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a non-linear, parabolic pattern. Patients with moderate baseline viral loads (5.00-7.99 log10 IU/mL) exhibited the highest HCC risk (HR, 2.60; p<0.001), followed by those with low viral loads (3.30-4.99 log10 IU/mL; HR, 1.66; p=0.11). Patients with high viral loads (≥8.00 log10 IU/mL) presented the lowest HCC risk. Particularly, patients with baseline HBV DNA levels 6.00-6.99 log10 IU/mL had the highest on-treatment HCC risk (HR, 3.36; p<0.001) compared with those with baseline HBV DNA levels≥8.00 log10 IU/mL. These findings were more prominent among HBeAg-positive patients, younger patients, or those with less advanced hepatic fibrosis. CONCLUSION: Patients with moderate baseline viral load, particularly around 6 log10 IU/mL, demonstrated the highest on-treatment HCC risk, despite long-term antiviral treatment. Early initiation of antiviral treatment, tailored to viral load, should be considered to minimise HCC risk in adult CHB patients without cirrhosis.

Association between statin use and the prognosis of hepatocellular carcinoma after resection: a nationwide cohort study.

Background: The majority of patients with hepatocellular carcinoma (HCC) following hepatic resection experience tumor recurrence. Statin use is associated with a reduced risk of HCC development; however, the association between statin use and the prognosis of HCC after resection remains unclear. We aimed to investigate the effect of statin use on the prognosis after hepatic resection among patients with HCC. Methods: A nationwide cohort study was performed with data from the National Health Insurance Service Database in Korea. Among 65,101 HCC patients who underwent hepatic resection between January 2002 and December 2017, we included 21,470 patients. For validation, a hospital-based cohort of 3366 patients with very early or early-stage HCC who received curative-intent hepatic resection between January 2010 and December 2018 was analyzed. Recurrence-free survival (RFS) and overall survival (OS) was compared between statin users and non-users. Findings: Among the nationwide cohort of 21,470 patients, 2399 (11.2%) used statins and 19,071 (88.8%) did not. Among the hospital cohort of 3366 patients, 363 (10.8%) used statins and 3003 (89.2%) did not. In the propensity score-matched nationwide cohort, statin users had better RFS (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.56-0.64; P < 0.001) and OS (HR, 0.49; 95% CI, 0.45-0.53; P < 0.001), with a duration-response relationship. In the propensity score-matched validation hospital cohort, statin treatment was significantly associated with better RFS (HR, 0.73; 95% CI, 0.59-0.90; P = 0.003) and OS (HR, 0.48; 95% CI, 0.32-0.72; P < 0.001). The beneficial effects of statins were more prominent in non-cirrhotics, tumors sized ≥3 cm, tumors with microscopic vascular invasion, or early HCC recurrence (<2 years after resection). Interpretation: Statin use was associated with a better prognosis in a population-based cohort of patients with HCC after hepatic resection, which was further validated in a large hospital-based cohort. Funding: Asan Institute for Life Sciences and Corporate Relations; Korean Association for the Study of the Liver.

Are the New Nucleos(t)ide Analogs Better than the Old Nucleos(t)ide Analogs?

In treatment-naïve patients with chronic hepatitis B virus (HBV) infection, entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide have a minimal or no risk of drug-resistance. These 3 nucleos(t)ide analog agents are highly potent inducing high rate of virologic response (reducing serum HBV DNA to levels undetectable by polymerase chain reaction assays) in most treatment-naïve patients. Our randomized trials have demonstrated that monotherapy with TDF can provide a successful virological response in most of the heavily pretreated patients with multidrug resistance to ETV or adefovir.

Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment.

Background/Aim: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. Methods: A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. Results: The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0-4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). Conclusions: Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

Clinical outcomes of immune checkpoint inhibitors in unresectable or metastatic combined hepatocellular-cholangiocarcinoma.

PURPOSE: Immune checkpoint inhibitors (ICIs) have been demonstrated to be effective for unresectable or metastatic hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA) in prior prospective trials. However, the clinical outcomes of ICIs in patients with combined HCC-CCA (cHCC-CCA) have not been investigated. Accordingly, we retrospectively evaluated the effectiveness and safety of ICIs in patients with unresectable or metastatic cHCC-CCA. METHODS: Among 101 patients with histologically documented cHCC-CCA who received systemic therapy, 25 received ICIs between January 2015 and September 2021 and were included in the current analysis. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were retrospectively evaluated. RESULTS: The median age was 64 years (range 38-83) and 84% (n = 21) of patients were males. Most patients had Child-Pugh A liver function (n = 22, 88%) and hepatitis B virus infection (17, 68%). Nivolumab (n = 17, 68%) was the most frequently used ICI, followed by pembrolizumab (n = 5, 20%), atezolizumab plus bevacizumab (n = 2, 8%), and ipilimumab plus nivolumab (n = 1, 4%). All patients, except one, had previously received systemic therapy; median two lines (1-5 lines) of systemic therapy were administered prior to ICIs. With a median follow-up duration of 20.1 months (95% CI 4.9-35.2 months), the median PFS was 3.5 months (95% CI 2.4-4.8 months), and the median OS was 8.3 months (95% CI 6.8-9.8 months). The ORR was 20.0% (n = 5, nivolumab for 2 patients, pembrolizumab for 1, atezolizumab plus bevacizumab for 1, and ipilimumab plus nivolumab for 1) and the duration of response was 11.6 months (95% CI 11.2-12.0 months). CONCLUSIONS: ICIs displayed clinical anti-cancer effectiveness, aligning with the results of prior prospective studies for HCC or CCA. Further international studies are required to define the optimal strategies for managing unresectable or metastatic cHCC-CCA.

Low Level of Hepatitis B Viremia Compared With Undetectable Viremia Increases the Risk of Hepatocellular Carcinoma in Patients With Untreated Compensated Cirrhosis.

INTRODUCTION: The initiation of antiviral treatment in patients with chronic hepatitis B with compensated cirrhosis and low-level viremia (LLV; HBV DNA 15-2,000 IU/mL) remains controversial. We sought to compare the long-term outcomes of these untreated patients according to their viremic status. METHODS: Six hundred twenty-seven untreated patients with chronic hepatitis B with compensated cirrhosis were analyzed retrospectively. The risk of hepatocellular carcinoma (HCC) and liver-related clinical events, including hepatic decompensation, were compared between patients with LLV and undetectable HBV DNA. Patients who received antiviral treatment were censored during treatment initiation. RESULTS: The mean age of the patients was 54.7 years, 64.4% of whom were male. During the study period, 59 patients developed HCC (20 and 39 in the undetectable and LLV groups, respectively) with an annual incidence of 2.44/100 person-years. Multivariable analysis revealed that the LLV group was associated with a significantly higher risk of HCC (adjusted hazard ratio: 2.36, P = 0.002) than the undetectable group. In the 204 propensity score-matched cohort, the LLV group had a 2.16-fold greater risk of HCC than the undetectable group ( P = 0.014). Liver-related clinical events occurred in 121 patients with an annual incidence of 5.25/100 person-years. Despite not reaching statistical significance, the LLV group tended to have a higher risk of liver-related events in the propensity score-matched cohort (hazard ratio: 1.14, P = 0.50). DISCUSSION: Compared with patients with undetectable HBV DNA, those with compensated cirrhosis and LLV had a significantly higher risk of HCC. Antiviral treatment should be advised for these patients.

Detecting Early Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Using Longitudinal α-Fetoprotein Screening.

BACKGROUND & AIMS: This study aimed to evaluate the parametric empirical Bayes (PEB) longitudinal α-fetoprotein (AFP) screening algorithm performance in patients with hepatitis B compared with AFP surveillance with a fixed threshold. METHODS: The serum AFP of 588 patients was measured. Patients were screened at least once every 6 months with AFP and ultrasound or computed tomography/magnetic resonance imaging. Age, aspartate aminotransferase level, alanine aminotransferase level, platelet count, total bilirubin, prothrombin time, and hepatitis B virus DNA level were adjusted in the PEB algorithm. All variables were abstracted at the time of hepatocellular carcinoma (HCC) diagnosis for cases or last follow-up for controls and at months -6, -12, -18, -24, -30, -36, -42, -48, and -54, up to month -60. RESULTS: Overall, 62 (10.5%) HCC cases developed during a median follow-up of 52.7 months. Moreover, 55 (88.7%) cases were detected at Barcelona Clinic Liver Cancer stage 0 or A. The area under the receiver-operating characteristic curve of the patient-level true positive rate against the screening-level false positive rate was significantly higher in the PEB algorithm than that in AFP alone (area under the receiver-operating characteristic curve: 0.94 vs 0.86; P < .0005). At 80% specificity, the PEB algorithm significantly improved the patient-level true positive rate within 2 years prior to HCC diagnosis compared with AFP alone (80.6% vs 67.7%, respectively; P = .0485; adjusted P = .1663). The PEB algorithm more effectively enabled first positive screening. CONCLUSIONS: The longitudinal assessment of AFP by the PEB algorithm improved HCC screening performance compared to AFP alone in patients with hepatitis B. This algorithm may improve HCC screening without additional cost or inconvenience to patients.

Impact of HBsAg seroclearance on late recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection.

BACKGROUND & AIMS: It is unknown whether HBsAg seroclearance affects the risk of hepatocellular carcinoma (HCC) recurrence after liver resection. We aimed to investigate the impact of HBsAg seroclearance on the recurrence of HCC after curative liver resection, with a focus on late recurrence. METHODS: This study comprised 2,520 consecutive patients who received curative liver resection for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A in Korea between 2000 and 2017. To focus on late recurrence, patients with recurrence or a follow-up duration less than 2 years were excluded. The impact of HBsAg seroclearance on HCC recurrence was assessed by landmark analysis (2-, 5-and 8-year after liver resection), time-dependent Cox and multistate modeling. RESULTS: The mean patient age was 54.4 years and 75.7% were men. A total of 891 (35.4%) patients developed HCC recurrence at rates of 11.2%, 25.5%, and 46.8% at 3, 5, and 10 years after resection. HBsAg seroclearance was achieved in 172 (6.8%) patients during a median follow-up duration of 6.9 years after resection. HBsAg seroclearance, compared with persistent HBsAg positivity, was associated with a lower risk of late HCC recurrence in the 2-, 5-, and 8-year landmark analysis (p = 0.04, p = 0.02 and p = 0.03, respectively) and on time-dependent multivariable Cox modeling (adjusted hazard ratio 0.62; p = 0.005). Based on a 3-state unidirectional illness-death model, patients without HBsAg seroclearance transitioned to HCC recurrence more rapidly than patients who experienced HBsAg seroclearance. CONCLUSIONS: HBsAg seroclearance is associated with a lower risk of late recurrence of HBV-related HCC among Korean patients who undergo curative liver resection. LAY SUMMARY: Hepatitis B virus (HBV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma (HCC). Suppression of HBV replication is known to lower the risk of HCC recurrence after liver resection (a procedure used to treat and in some cases cure HCC). However, whether the loss of a specific HBV protein (hepatitis B surface antigen or HBsAg) has an impact on recurrence after liver resection remains unknown. Herein, we show that loss of HBsAg is associated with a reduce risk of late recurrence of HCC after liver resection in patients with HBV-related HCC.

Real-world efficacy and safety of cabozantinib in Korean patients with advanced hepatocellular carcinoma: a multicenter retrospective analysis.

Background: Cabozantinib, a multiple kinase inhibitor, was recently approved for patients with previously treated unresectable hepatocellular carcinoma (uHCC). We investigated the real-world safety and efficacy profiles of cabozantinib. Methods: This multicenter retrospective study included 110 patients with uHCC who received cabozantinib after progression on other systemic treatments between October 2019 and May 2021. Results: The median age was 58 (range, 20-77) years, and 98 (89.1%) were male. Prior to cabozantinib, all patients were treated with other systemic therapies: sorafenib (n = 104, 94.5%) and regorafenib (n = 91, 82.7%) were the most commonly used agents. Immune checkpoint inhibitors were previously used in 93 patients (84.5%). Cabozantinib was used beyond the third-line of therapy in most patients (n = 90, 81.8%). With a median follow-up duration of 11.9 months [95% confidence interval (CI), 10.8-17.2], the median progression-free survival (PFS) was 3.7 months (95% CI, 3.1-4.9), and the median overall survival (OS) was 7.5 months (95% CI, 5.5-9.5). The disease control rate and overall response rate (ORR) were 66.3% and 3.6%, respectively. In the Child-Pugh A cohort (n = 88), the ORR was 4.5%, and the median PFS and OS were 4.3 months (95% CI, 3.6-5.8) and 9.0 months (95% CI, 7.5-11.7), respectively. Conclusion: Cabozantinib showed consistent efficacy outcomes with a prior phase III trial, although in this study, it was used as later-line therapy for patients who were refractory to multiple systemic treatments, including immune checkpoint inhibitors.

Radiologic Response as a Prognostic Factor in Advanced Hepatocellular Carcinoma with Macroscopic Vascular Invasion after Transarterial Chemoembolization and Radiotherapy.

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.

Identification of hepatic steatosis in living liver donors by machine learning models.

Selecting an optimal donor for living donor liver transplantation is crucial for the safety of both the donor and recipient, and hepatic steatosis is an important consideration. We aimed to build a prediction model with noninvasive variables to evaluate macrovesicular steatosis in potential donors by using various prediction models. The study population comprised potential living donors who had undergone donation workup, including percutaneous liver biopsy, in the Republic of Korea between 2016 and 2019. Meaningful macrovesicular hepatic steatosis was defined as >5%. Whole data were divided into training (70.5%) and test (29.5%) data sets based on the date of liver biopsy. Random forest, support vector machine, regularized discriminant analysis, mixture discriminant analysis, flexible discriminant analysis, and deep neural network machine learning methods as well as traditional logistic regression were employed. The mean patient age was 31.4 years, and 66.3% of the patients were men. Of the 1652 patients, 518 (31.4%) had >5% macrovesicular steatosis on the liver biopsy specimen. The logistic model had the best prediction power and prediction performances with an accuracy of 80.0% and 80.9% in the training and test data sets, respectively. A cut-off value of 31.1% for the predicted risk of hepatic steatosis was selected with a sensitivity of 77.7% and specificity of 81.0%. We have provided our model on the website (https://hanseungbong.shinyapps.io/shiny_app_up/) under the name DONATION Model. Our algorithm to predict macrovesicular steatosis using routine parameters is beneficial for identifying optimal potential living donors by avoiding superfluous liver biopsy results.