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Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.
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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.
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Carcinoma Hepatocelular , Guanina/análogos & derivados , Hepatitis B Crónica , Neoplasias Hepáticas , Organofosfonatos , Humanos , Tenofovir/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Antivirales/uso terapéutico , Adenina , Neoplasias Hepáticas/tratamiento farmacológico , AlaninaRESUMEN
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.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Estadificación de Neoplasias , Pronóstico , Hepatectomía , Puntaje de PropensiónRESUMEN
BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.
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Várices Esofágicas y Gástricas , Várices , Humanos , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/prevención & control , Hemorragia Gastrointestinal , Ligadura , Antagonistas Adrenérgicos beta/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Várices/tratamiento farmacológicoRESUMEN
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.
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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.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Masculino , Humanos , Persona de Mediana Edad , Femenino , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/tratamiento farmacológico , Antivirales/uso terapéutico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , Tenofovir/uso terapéutico , Estudios RetrospectivosRESUMEN
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.
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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.
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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%. 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.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Trombosis , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/terapia , Sorafenib/uso terapéutico , Neoplasias Hepáticas/patología , Vena Porta/patología , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Trombosis/terapia , Resultado del Tratamiento , Quimioembolización Terapéutica/métodosRESUMEN
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.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Persona de Mediana Edad , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Virus de la Hepatitis B , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
BACKGROUND: Advanced endoscopic retrograde cholangiopancreatography (ERCP) cannulation strategies for difficult cases could replace conventional techniques, in which assistants control guidewires. We aimed to compare the safety and efficacy of a new salvage cannulation strategy, physician-controlled wire-guided cannulation (PCWGC), with those of a conventional strategy. METHODS: This retrospective study included patients with naïve papillae who underwent ERCP between January 2018 and December 2020. Patients, divided into two groups, received initial cannulation using a conventional catheter. After failed cannulation, the second attempt used PCWGC and double-guidewire technique (DGT) in the new and conventional strategy groups, respectively. Propensity score-matching (PSM) analysis compared outcomes between groups. Primary outcome included overall success rate, while secondary outcomes included cannulation time, adverse events, and cannulation difficulty subgroup analysis. RESULTS: The new strategy group comprised 255 (47.6%) of 536 patients who underwent ERCP. The total cannulation success rate was 98.4% (vs. 97.2%, p = 0.318), with similar post-ERCP pancreatitis (PEP) (1.8% vs. 2.4%, p = 0.64) rates. Following 1:1 PSM, 219/438 patients were allocated to both the conventional and new strategy groups, and 46 patients from the difficult cannulation subgroup were distributed evenly among groups. No difference in overall cannulation success rate existed between the groups before (97.2% vs. 98.4%) and after PSM (96.8% vs. 98.2%). The primary cannulation success rate was higher in the conventional strategy group, while the secondary cannulation success rate was higher in the new strategy group. However, the difficult cannulation subgroup PSM results showed that only the salvage cannulation success rate was significant (9/23, 39.1% vs. 18/23, 78.3%, p = 0.007). In the difficult cannulation subgroup, the salvage cannulation success rate for PCWGC was four times higher than DGT (95% confidence interval; 1.129-14.175), with no significant difference in PEP rate (p = 0.571). CONCLUSIONS: PCWGC demonstrated greater efficacy than the conventional salvage technique. PCWGC could be a safe and useful technique, especially for difficult biliary cannulation.
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Cateterismo , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudios Retrospectivos , Puntaje de Propensión , Cateterismo/efectos adversos , Cateterismo/métodos , Catéteres , Esfinterotomía Endoscópica , Resultado del TratamientoRESUMEN
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.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Masculino , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/prevención & control , Carcinoma Hepatocelular/complicaciones , Inteligencia Artificial , Neoplasias Hepáticas/complicaciones , Resultado del Tratamiento , Tenofovir/uso terapéutico , Aprendizaje Automático , Virus de la Hepatitis B , Estudios RetrospectivosRESUMEN
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.
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Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Hepatitis B Crónica/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Pronóstico , Antígenos e de la Hepatitis B , Albúminas , Virus de la Hepatitis B/genética , Alanina Transaminasa , ADN ViralRESUMEN
INTRODUCTION: For the treatment of spontaneous bacterial peritonitis (SBP), cefotaxime, ceftriaxone, and ciprofloxacin were used as first-line agents. However, considering the increasing rate of antibiotic resistance, it is unclear which of these drugs can be initially recommended. This study aimed to compare the current efficacy of the 3 antibiotics, namely cefotaxime, ceftriaxone, and ciprofloxacin, for the treatment of SBP in patients with cirrhosis with ascites, when guided by therapeutic responses. METHODS: This study was a multicenter, prospective, randomized controlled trial. The inclusion criteria were 16- to 75-year-old patients with liver cirrhosis with ascites, having polymorphonuclear cell count of >250/mm 3 . We performed a follow-up paracentesis at 48 hours to decide continuing or changing the assigned antibiotics and then assessed the resolution rates at 120 and 168 hours of treatment. RESULTS: A total of 261 patients with cirrhosis who developed SBP were enrolled. Most of the patients were diagnosed as those with SBP within 48 hours of admission. The resolution rates at 120 hours, which is the primary endpoint, were 67.8%, 77.0%, and 73.6% in the cefotaxime, ceftriaxone, and ciprofloxacin groups, respectively ( P = 0.388), by intension-to-treat analysis. The 1-month mortality was similar among the groups ( P = 0.770). The model for end-stage liver disease score and the SBP resolution were significant factors for survival. CONCLUSION: The efficacy of empirical antibiotics, such as cefotaxime, ceftriaxone, and ciprofloxacin, against SBP was not significantly different. In addition, these antibiotics administered based on response-guided therapy were still efficacious as initial treatment for SBP, especially in those with community-acquired infections.
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Infecciones Bacterianas , Enfermedad Hepática en Estado Terminal , Peritonitis , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Cefotaxima/uso terapéutico , Ceftriaxona/uso terapéutico , Ciprofloxacina/uso terapéutico , Ascitis/tratamiento farmacológico , Estudios Prospectivos , Enfermedad Hepática en Estado Terminal/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Antibacterianos/uso terapéutico , Peritonitis/tratamiento farmacológico , Peritonitis/etiología , Peritonitis/diagnóstico , Cirrosis Hepática/terapia , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiologíaRESUMEN
Background: Serum asialo α1-acid gycoprotein (AsAGP) is a novel biomarker specific to liver fibrosis. Aim: To evaluate the diagnostic efficacy of serum AsAGP levels in classifying the severity of liver fibrosis and differentiating liver cirrhosis (LC) in patients with chronic hepatitis B (CHB) from healthy controls. Methods: Overall, 206 subjects were prospectively enrolled. LC was diagnosed based on liver stiffness levels (>11 kPa) measured using transient elastography. Serum AsAGP levels were measured using an antibody-lectin sandwich immunoassay. We investigated the diagnostic performance by comparing serum AsAGP levels among healthy control, CHB, and CHB with LC groups. Sensitivity, specificity, and optimal AsAGP cut-off values were also calculated. Results: Serum AsAGP levels were significantly different between healthy controls, CHB patients, and CHB patients with LC (1.04 ± 0.31 µg/mL, 1.12 ± 0.34 µg/mL, 1.51 ± 0.43 µg/mL respectively; p < 0.001). Serum AsAGP levels positively correlated with liver stiffness (r = 0.46, p < 0.001). AUROC of healthy control versus CHB with LC was 0.821 (p < 0.001, optimal cut-off 1.036 µg/mL). AUROC of healthy control versus CHB was 0.624 (p = 0.049, optimal cut-off level 0.934 µg/mL). AUROC of CHB versus CHB with LC was 0.765, (p < 0.001, optimal cut-off 1.260 µg/mL). Conclusions: Serum AsAGP levels in CHB patients with LC were significantly higher than those in healthy controls and CHB patients. AsAGP levels showed good diagnostic performance in predicting advanced fibrosis and cirrhosis, which suggests a potential role as a biomarker for predicting the progression of liver disease in CHB.
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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.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , Humanos , Virus de la Hepatitis B/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/diagnóstico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , ADN Viral , Cirrosis Hepática/etiología , Antivirales/uso terapéutico , Antivirales/farmacología , Estudios Retrospectivos , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológicoRESUMEN
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.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Neoplasias Hepáticas/epidemiología , Hepatitis B Crónica/complicaciones , Antígenos e de la Hepatitis B , Cirrosis Hepática/etiologíaRESUMEN
Background/Aims: We investigated the factors related to spleen length and the diagnostic accuracy of a model using spleen length corrected by related factors, for the prediction of varices needing treatment (VNT). Methods: Various prediction models for VNT including spleen length were analyzed in the cohort of compensated advanced chronic liver disease (cACLD), defined as liver stiffness (LS) ≥10 kPa in a recent study. The associated factors for spleen length were identified in healthy subjects to improve the prediction of VNT. Results: Among 1,218 cACLD patients, VNT was noted in 249 patients (20.4%). On multivariate analysis, longer spleen length, lower platelet count, and higher LS value were independent predictors for VNT (all p<0.001). In multivariate analysis of 1,041 healthy subjects, age (ß=-0.027), sex (ß=0.762), and body mass index (ß=0.097) were found to be significant factors for spleen length (all p<0.001). Using the ß values, the estimated spleen length was calculated. To improve the prediction of VNT, the ratio of measured and estimated spleen length was calculated. Based on binary regression analysis results, the LS value-spleen ratio to platelet score (LSRPS) was calculated as follows: 0.027×LS value (kPa)+2.690×measured/estimated spleen ratio-0.011×platelet count (cells×109/L)-4.215. The area under the receiver operating characteristic of the LSRPS for VNT was 0.820, which was significantly higher than 0.797 of LS value-spleen diameter to platelet ratio score (LSPS) (p=0.006). Conclusions: Spleen length is influenced by age, sex, and body mass index in the Asian population. The LSRPS using the measured/estimated spleen ratio had higher diagnostic accuracy than LSPS in predicting VNT in patients with cACLD.
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Diagnóstico por Imagen de Elasticidad , Várices Esofágicas y Gástricas , Hipertensión Portal , Humanos , Cirrosis Hepática/patología , Bazo/diagnóstico por imagen , Índice de Masa Corporal , Várices Esofágicas y Gástricas/patología , Valor Predictivo de las Pruebas , Hígado/diagnóstico por imagen , Hígado/patología , Diagnóstico por Imagen de Elasticidad/métodosRESUMEN
BACKGROUND: The European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium suggested that the clinical courses after acute decompensation (AD) stratify the long-term prognosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre acute-on-chronic liver failure (pre ACLF), and ACLF. However, previous studies included patients with a history of previous AD and had limitations associated with identifying the clinical factors related to prognosis after the first AD. METHOD: The prospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort included cirrhotic patients who were hospitalised with first AD between July 2015 and August 2018. We analysed the factors associated with readmission after the first AD and compared the characteristics and prognosis among each subgroup to evaluate the risk factors for the occurrence of pre ACLF after AD. RESULT: A total of 746 cirrhotic patients who were hospitalised with first AD were enrolled. The subgroups consisted of SDC (n = 565), UDC (n = 29), pre ACLF (n = 28), and ACLF (n = 124). Of note, pre ACLF showed a poorer prognosis than ACLF. The risk factors associated with readmission within 3 months of first AD were non-variceal gastrointestinal (GI) bleeding, hepatic encephalopathy (HE), and high MELD score. Viral aetiology was associated with the occurrence of pre ACLF compared with alcohol aetiology regardless of baseline liver function status. CONCLUSION: Cirrhotic patients with first AD who present as non-variceal GI bleeding and HE can easily relapse. Interestingly, the occurrence of AD with organ failure within 3 months of first AD (pre ACLF) has worse prognosis compared with the occurrence of organ failure at first AD (ACLF). In particular, cirrhotic patients with viral hepatitis with/without alcohol consumption showed poor prognosis compared to other aetiologies. Therefore, patients with ACLF after AD within 3 months should be treated more carefully and definitive treatment through LT should be considered.
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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.