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Background/Aims@#Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment. @*Methods@#Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders. @*Results@#The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.01, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88–1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60–0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81–0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62–0.75, P<0.01; E-value for SHR=2.30). @*Conclusions@#TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.
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Background/Aims@#This study aimed to assess whether hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) could have favorable prognoses with proper treatment under selective conditions. @*Methods@#This retrospective, single-center study involved 1,168 patients diagnosed with HCC between January 2005 and December 2006, before the introduction of sorafenib. Overall survival (OS) was estimated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify and adjust the variables associated with OS. @*Results@#In nodular-type HCC, the OS differed significantly according to the presence of PVTT (log-rank p<0.001), and the level of PVTT, not only its presence, was a major independent factor affecting OS. PVTT at the Vp1-3 branch was associated with significantly longer OS than was PVTT at the Vp4 level (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.04 to 3.21). In multivariate analysis, the OS was further stratified according to the PVTT level and tumor type, representing that nodular HCC without PVTT exhibited the best OS, whereas nodular HCC with Vp4 PVTT (adjusted HR, 2.59; 95% CI, 1.57 to 4.28) showed a poor prognosis similar to that of infiltrative HCC. The PVTT level was consistently correlated with OS in patients treated with transarterial chemoembolization. Nodular HCC without PVTT showed the best prognosis, while nodular HCC with Vp1-3 PVTT also exhibited a favorable OS, although inferior to that without PVTT (adjusted HR, 1.47, 95% CI, 0.92 to 2.36). @*Conclusions@#Active treatment such as transarterial chemoembolization can be considered for selected PVTT cases. The level of PVTT and type of HCC were independent prognostic factors.
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Background@#/Aim: Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT). @*Methods@#We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1. @*Results@#A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74). @*Conclusion@#The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.
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Objective@#To evaluate the therapeutic outcomes of no-touch radiofrequency ablation (NT-RFA) using twin cooled wet (TCW) electrodes in patients experiencing recurrent hepatocellular carcinoma (HCC) after undergoing locoregional treatments. @*Materials and Methods@#We conducted a prospective, single-arm study of NT-RFA involving 102 patients, with a total of 112 recurrent HCCs (each ≤ 3 cm). NT-RFA with TCW electrodes was implemented under the guidance of ultrasonography (US)-MR/CT fusion imaging. If NT-RFA application proved technically challenging, conversion to conventional tumor puncture RFA was permitted. The primary metric for evaluation was the mid-term cumulative incidence of local tumor progression (LTP) observed post-RFA. Cumulative LTP rates were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazard regression was used to explore factors associated with LTP. Considering conversion cases from NT-RFA to conventional RFA, intention-to-treat (ITT; including all patients) and per-protocol (PP; including patients not requiring conversion to conventional RFA alone) analyses were performed. @*Results@#Conversion from NT-RFA to conventional RFA was necessary for 24 (21.4%) out of 112 tumors. Successful treatment was noted in 111 (99.1%) out of them. No major complications were reported among the patients. According to ITT analysis, the estimated cumulative incidences of LTP were 1.9%, 6.0%, and 6.0% at 1, 2, and 3 years post-RFA, respectively. In PP analysis, the cumulative incidence of LTP was 0.0%, 1.3%, and 1.3% at 1, 2, and 3 years, respectively. The number of previous locoregional HCC treatments (adjusted hazard ratio [aHR], 1.265 per 1 treatment increase; P = 0.004), total bilirubin (aHR, 7.477 per 1 mg/dL increase; P = 0.012), and safety margin ≤ 5 mm (aHR, 9.029; P = 0.016) were independently associated with LTP in ITT analysis. @*Conclusion@#NT-RFA using TCW electrodes is a safe and effective treatment for recurrent HCC, with 6.0% (ITT analysis) and 1.3% (PP analysis) cumulative incidence of LTP at 2 and 3-year follow-ups.
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Background@#/Aim: To evaluate the applicability of transarterial chemoembolization (TACE) treatment with doxorubicin drug-eluting beads (DEBs) in advanced hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). @*Methods@#This prospective study was approved by the institutional review board and informed consent was obtained from all participants. A total of 30 HCC patients with PVI received DEB-TACE between 2015 and 2018. The following parameters were evaluated: complications during DEB-TACE, abdominal pain, fever, and laboratory outcomes, including liver function change. Overall survival (OS), time to progression (TTP), and adverse events were also analyzed and assessed. @*Results@#DEBs measuring 100–300 μm in diameter were loaded with doxorubicin (150 mg per procedure). There were no complications during DEB-TACE and no significant differences in the levels of prothrombin time, serum albumin, or total bilirubin at follow-up compared to baseline. The median TTP was 102 days (95% confidence interval [CI], 42–207 days) and the median OS was 216 days (95% CI, 160–336 days). Three patients (10%) had severe adverse reactions, including transient acute cholangitis (n=1), cerebellar infarction (n=1), and pulmonary embolism (n=1), but no treatment-related death occurred. @*Conclusions@#DEB-TACE may be a therapeutic option for advanced HCC patients with PVI.
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Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.
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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%. @*Conclusions@#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.
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Background/Aims@#Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients. @*Methods@#This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively. @*Results@#Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6–69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29–0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26–0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33–0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32–0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively. @*Conclusions@#Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.
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Background@#Rituximab occasionally induces reactivation of hepatitis B virus (HBV) in patients with resolved HBV, at times with fatal consequences. The optimal duration of prophylactic antiviral therapy in this situation is unclear. We aimed to investigate the difference in HBV reactivation according to the duration of prophylactic tenofovir disoproxil fumarate (TDF) in patients with resolved HBV and receiving rituximab. @*Methods@#A multicenter, randomized, open-label, prospective study was conducted in hepatitis B surface antigen-negative and anti-HBc-positive non-Hodgkin’s lymphoma patients treated with rituximab-based chemotherapy. A total of 90 patients were randomized and received prophylactic TDF from the initiation of rituximab until 6 months (the 6-month group) or 12 months (the 12-month group) after the completion of rituximab. The primary outcome was the difference in HBV reactivation and the secondary outcomes were the difference in hepatitis flare and adverse events between the two groups. @*Results@#In an intention to treat (ITT) analysis, HBV reactivation occurred in 1 of 43 patients (2.3%; 95% confidence interval [CI], 0.41–12%) at a median of 13.3 months in the 6-month group and 2 of 41 patients (4.9%; 95% CI, 1.4–16%) at a median of 13.7 months in the 12-month group. In a per protocol (PP) analysis, HBV reactivation occurred in 1 of 18 patients (5.6%; 95% CI, 0.99–26%) at 13.3 months in the 6-month group and 1 of 13 patients (7.7%; 95% CI, 1.4–33%) at 9.7 months in the 12-month group. The cumulative incidence of HBV reactivation was not significantly different between the two groups in ITT and PP analyses (P = 0.502 and 0.795, respectively). The occurrence of adverse events was not significantly different between the two groups in ITT (9.3% in the 6-month group, 22.0% in the 12-month group, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999). @*Conclusion@#Prophylactic TDF up to 6 months after completion of rituximab-based chemotherapy is sufficient in terms of the efficacy and safety of reducing HBV reactivation in patients with resolved HBV.Trial Registration: ClinicalTrials.gov Identifier: NCT02585947
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Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1–30 days post-vaccination compared to baseline (median, −21.4 IU/ml from baseline), but the levels reverted to baseline by 91–180 days (median, −3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: −0.06, −0.39, and −0.04 log 10 IU/ml/year in pre-vaccination period, days 1–30, and days 31–90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, −13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A + NK cells was observed in the CD56dimCD16+ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A + NK cells.
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The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.
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Background/Aims@#Glecaprevir/pibrentasvir (G/P) is the first pan-genotypic direct-acting antiviral combination therapy approved in Korea. An integrated analysis of five phase II and III trials was conducted to evaluate the efficacy and safety of G/P in Korean patients with chronic hepatitis C virus (HCV) infection. @*Methods@#The study analyzed pooled data on Korean patients with HCV infection enrolled in the ENDURANCE 1 and 2, SURVEYOR II part 4 and VOYAGE I and II trials, which evaluated the efficacy and safety of 8 or 12 weeks of G/P treatment. The patients were either treatment-naïve or had received sofosbuvir or interferon-based treatment. Efficacy was evaluated by assessing the rate of sustained virologic response at 12 weeks posttreatment (SVR12). Safety was evaluated by monitoring adverse events (AEs) and laboratory assessments. @*Results@#The analysis included 265 patients; 179 (67.5%) were HCV treatment-naïve, and most patients were either subgenotype 1B (48.7%) or 2A (44.5%). In the intention-to-treat population, 262 patients (98.9%) achieved SVR12. Three patients did not achieve SVR12: one had virologic failure and two had non-virologic failures. Most AEs were grade 1/2; eight patients (3.0%) expe-rienced at least one grade ≥3 AE. No serious AEs related to G/P treatment were reported, and grade ≥3 hepatic laboratory abnormalities were rare (0.8%). @*Conclusions@#G/P therapy was highly efficacious and well tolerated in Korean patients with HCV infection, with most patients achieving SVR12. The safety profile was comparable to that observed in a pooled analysis of a global pan-genotypic population of patients with HCV infection who received G/P.
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Objective@#This study aimed to compare the efficacy between no-touch (NT) radiofrequency ablation (RFA) and conventional RFA using twin internally cooled wet (TICW) electrodes in the bipolar mode for the treatment of small hepatocellular carcinomas (HCC). @*Materials and Methods@#In this single-center, two-arm, parallel-group, prospective randomized controlled study, we performed a 1:1 random allocation of eligible patients with HCCs to receive NT-RFA or conventional RFA between October 2016 and September 2018. The primary endpoint was the cumulative local tumor progression (LTP) rate after RFA. Secondary endpoints included technical conversion rates of NT-RFA, intrahepatic distance recurrence, extrahepatic metastasis, technical parameters, technical efficacy, and rates of complications. Cumulative LTP rates were analyzed using Kaplan-Meier analysis and the Cox proportional hazard regression model. Considering conversion cases from NT-RFA to conventional RFA, intentionto-treat and as-treated analyses were performed. @*Results@#Enrolled patients were randomly assigned to the NT-RFA group (37 patients with 38 HCCs) or the conventional RFA group (36 patients with 38 HCCs). Among the NT-RFA group patients, conversion to conventional RFA occurred in four patients (10.8%, 4/37). According to intention-to-treat analysis, both 1- and 3-year cumulative LTP rates were 5.6%, in the NT-RFA group, and they were 11.8% and 21.3%, respectively, in the conventional RFA group (p = 0.073, log-rank). In the as-treated analysis, LTP rates at 1 year and 3 years were 0% and 0%, respectively, in the NT-RFA group sand 15.6% and 24.5%, respectively, in the conventional RFA group (p = 0.004, log-rank). In as-treated analysis using multivariable Cox regression analysis, RFA type was the only significant predictive factor for LTP (hazard ratio = 0.061 with conventional RFA as the reference, 95% confidence interval = 0.000–0.497; p = 0.004). There were no significant differences in the procedure characteristics between the two groups. No procedure-related deaths or major complications were observed. @*Conclusion@#NT-RFA using TICW electrodes in bipolar mode demonstrated significantly lower cumulative LTP rates than conventional RFA for small HCCs, which warrants a larger study for further confirmation.
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Objective@#This study aimed to prospectively compare the efficacy, safety, and mid-term outcomes of dual-switching monopolar (DSM) radiofrequency ablation (RFA) to those of conventional single-switching monopolar (SSM) RFA in the treatment of hepatocellular carcinoma (HCC). @*Materials and Methods@#This single-center, two-arm, parallel-group, randomized controlled study was approved by the Institutional Review Board. Written informed consent was obtained from all patients upon enrollment. A total of 80 patients with 94 HCC nodules were randomized into either the DSM-RFA group or SSM-RFA group in a 1:1 ratio, using a blocked randomization method (block size 2). The primary endpoint was the minimum diameter of the ablation zone per unit time.The secondary endpoints included other technical parameters, complication rate, technique efficacy, and 2-year clinical outcomes. @*Results@#Significantly higher ablation energy per unit time was delivered to the DSM-RFA group than to the SSM-RFA group (1.7 ± 0.2 kcal/min vs. 1.2 ± 0.3 kcal/min; p< 0.001). However, no significant differences were observed between the two groups for the analyzed variables, including primary endpoint, regarding size of the ablation zone and ablation time. Major complication rates were 4.9% in the DSM-RFA group and 2.6% in the SSM-RFA group (p = 1.000). The 2-year local tumor progression (LTP) rates of the HCC nodules treated using DSM-RFA and SSM-RFA were 8.5% and 4.7%, respectively (p = 0.316).The 2-year LTP-free survival rates of patients in the DSM-RFA and SSM-RFA groups were 90.0% and 94.4%, respectively (p = 0.331), and the 2-year recurrence-free survival rates were 54.9% and 75.7%, respectively (p = 0.265). @*Conclusion@#Although DSM-RFA using a separable clustered electrode delivers higher ablation energy than SSM-RFA, its effectiveness failed to show superiority over SSM-RFA in the treatment of HCC.
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Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).
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Objective@#To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC). @*Materials and Methods@#This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and perlesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed. @*Results@#The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%). @*Conclusion@#DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.
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Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).
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Objective@#To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC). @*Materials and Methods@#This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and perlesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed. @*Results@#The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%). @*Conclusion@#DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.
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Background/Aims@#Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients. @*Methods@#Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias. @*Results@#Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0–10.8) months for regorafenib and 5.9 (95% CI, 3.7–8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30–0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51–1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04). @*Conclusions@#After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.
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Background/Aims@#Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis due to the lack of effective systemic therapies. Epithelial-to-mesenchymal transition (EMT) is a pivotal event in tumor progression, during which cancer cells acquire invasive properties. In this study, we investigated the effects of phosphatidylinositol 3-kinase (PI3K) inhibitors, including LY294002 and idelalisib, on the EMT features of HCC cells in vitro. @*Methods@#Human HCC cell lines, including Huh-BAT and HepG2, were used in this study. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and cell cycle distributions were evaluated using a flow cytometer by propidium iodide staining. Immunofluorescence staining, quantitative real-time polymerase chain reaction, and immunoblotting were performed to detect EMT-associated changes. @*Results@#PI3K inhibitors suppressed the proliferation and invasion of HCC cells and deregulated the expression of EMT markers, as indicated by increased expression of E-cadherin, an epithelial marker, and decreased expression of N-cadherin, a mesenchymal marker, and Snail, a transcription factor implicated in EMT regulation. Furthermore, LY294002 and idelalisib inhibited the phosphorylation of GSK-3β and induced the nuclear translocation of GSK-3β, which corresponded to the downregulation of Snail and β-catenin expressions in Huh-BAT and HepG2 cells. @*Conclusions@#The inhibition of PI3K/Akt signaling decreases Snail expression by enhancing the nuclear translocation of GSK-3β, which suppresses EMT in HCC cells, suggesting the potential clinical application of PI3K inhibitors for HCC treatment.