Publications by authors named "Young-Suk Lim"

269 Publications

Role of Tumor Biomarkers in the Surveillance of Hepatocellular Carcinoma.

Authors:
Young-Suk Lim

Korean J Gastroenterol 2021 Nov;78(5):284-288

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Biomarkers are key components of the clinical management of cancer patients because they have contributed to significant survival improvements in these patients. They allow the classification of patients based on common features and facilitate risk stratification, early detection, diagnosis, and prediction of the prognosis or treatment response. In hepatocellular carcinoma (HCC), there are few biomarkers incorporated in clinical practice. Despite this, this has been an extensive area of research in recent years, with increasing efforts to identify the biomarkers across the cancer care continuum from risk stratification to early detection to prognostication and treatment response. The heterogeneous nature of HCCs has restricted the performance of biomarkers. HCC biomarkers have limited roles in risk stratification, diagnosis, and treatment response. Currently, the main role of biomarkers is in the surveillance of HCC to detect it at an earlier stage and reduce mortality, which is the focus of this review.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4166/kjg.2021.137DOI Listing
November 2021

Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients.

Liver Int 2021 Nov 24. Epub 2021 Nov 24.

Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.

Background & Aims: We aimed to compare the performance of gadoxetic acid-enhanced abbreviated MRI (AMRI)-based surveillance and ultrasound-only surveillance in high-risk patients for hepatocellular carcinoma (HCC).

Methods: Prospectively recruited high-risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid-enhanced MRI (CMRI) and ultrasound at 6-months intervals were retrospectively analysed. AMRI consisted of diffusion-weighted, T2-weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI-only (AAA), and ultrasound-only (US) were compared using generalized estimating equations. Image quality was assessed.

Results: In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early-stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% [12/43]; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% [967/1012]; P = 0.01) and not significantly different from US (96.3% [975/1012]; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% [1004/1055]; P = 0.01) and the US approach (93.6% [987/1055]; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach.

Conclusions: In high-risk patients, AMRI-based surveillance approaches had higher sensitivities than ultrasound-only surveillance for early-stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI-only or ultrasound-only approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15110DOI Listing
November 2021

A risk scoring system to predict clinical events in chronic hepatitis B virus infection: A nationwide cohort study.

J Viral Hepat 2021 Nov 11. Epub 2021 Nov 11.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Many patients with chronic hepatitis B do not receive adequate follow-up. This study aimed to develop a risk score to predict clinical events in patients with chronic hepatitis B virus (HBV) infection at the population level for identifying patients at high risk to warrant regular follow-up. This study analysed population-based data from the nationwide claims database of South Korea obtained between 2005 and 2015. We identified 507,239 non-cirrhotic patients with chronic HBV infection who are not under antiviral treatment. A risk score for predicting clinical events (hepatocellular carcinoma, death or liver transplantation) was developed based on multivariable Cox proportional hazard model in a development cohort (n = 401,745) and validated in a validation cohort (n = 105,494). The cumulative incidence rates of clinical events at 5 years were 2.56% and 2.44% in the development and validation cohorts, respectively. Clinical events in asymptomatic patients with chronic HBV infection (CAP-B) score ranging from 0 to 7.5 points based on age, sex, socioeconomic status, chronic hepatitis C co-infection, diabetes mellitus, statin or antiplatelet exposure, smoking, alcohol consumption, alanine aminotransferase and gamma-glutamyltransferase had good discriminatory accuracy in both the development and validation cohorts (c-indices for 3-, 5- and 10-year risk prediction: all 0.786). The predicted and observed probabilities of clinical events were calibrated in both cohorts. A score of >3.5 points identified subjects at distinctly high risk. The CAP-B score using easily accessible variables can predict clinical events and may allow selection of patients with chronic HBV infection for priority of regular follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvh.13631DOI Listing
November 2021

The role of muscle depletion and visceral adiposity in HCC patients aged 65 and over undergoing TACE.

BMC Cancer 2021 Oct 30;21(1):1164. Epub 2021 Oct 30.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 44-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Background: The incidence of hepatocellular carcinoma (HCC) has been increasing among the elderly populations. Trans-arterial chemoembolization (TACE), a widely used first-line non-curative therapy for HCCs is an issue in geriatrics. We investigated the prognosis of elderly HCC patients treated with TACE and determined the factors that affect the overall survival.

Methods: We included 266 patients who were older than 65 years and had received TACE as initial treatment for HCC. We analyzed the skeletal muscle index (SMI) and visceral-to-subcutaneous fat ratio (VSR) around the third lumbar vertebrae using computed tomography scans. Muscle depletion with visceral adiposity (MDVA) was defined by falling below the median SMI and above the median VSR value sex-specifically. We evaluated the overall survival in association with MDVA and other clinical factors.

Results: The mean age was 69.9 ± 4.5 years, and 70.3% of the patients were men. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, 29, 136, and 101 patients were classified as BCLC 0, A, and B stages, respectively, and 79 (29.7%) had MDVA. During the median follow-up of 4.1 years, patients with MDVA had a shorter life expectancy than those without MDVA (P = 0.007) even though MDVA group had a higher objective response rate after the first TACE (82.3% vs. 75.9%, P = 0.035). Multivariate analysis revealed that MDVA (Hazard ratio [HR] 1.515) age (HR 1.057), liver function (HR 1.078), tumor size (HR 1.083), serum albumin level (HR 0.523), platelet count (HR 0.996), tumor stage (stage A, HR 1.711; stage B, HR 2.003), and treatment response after the first TACE treatment (HR 0.680) were associated with overall survival.

Conclusions: MDVA is a critical prognostic factor for predicting survival in the elderly patients with HCC who have undergone TACE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08905-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557070PMC
October 2021

A New Reporting System for Diagnosis of Hepatocellular Carcinoma in Chronic Hepatitis B With Clinical and Gadoxetic Acid-Enhanced MRI Features.

J Magn Reson Imaging 2021 Oct 20. Epub 2021 Oct 20.

Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Background: Current major guidelines for diagnosis of hepatocellular carcinoma (HCC) based on imaging findings are different from each other and do not include clinical risk factors as a diagnostic criteria.

Purpose: To developed and validated a new diagnostic score system using MRI and clinical features as applied in chronic hepatitis B patients.

Study Type: Retrospective observational study.

Subject: A total of 418 treatment-naïve patients (out of 902 patients) with chronic hepatitis B having 556 lesions suspected for HCC which were eligible for curative treatment.

Field Strength/sequence: T1W GRE in- and opposed-phase, T2W FSE, DWI, and T1W 3D-GRE dynamic contrast-enhanced sequences at 1.5  T and 3  T.

Assessment: Six radiologists with 7-22 years of experience independently evaluated MR images based on Liver Imaging Reporting and Data System (LI-RADS) version 2018.

Statistical Tests: Based on logistic regression analysis of MRI features and clinical factors, a risk score system was devised in derivation cohorts (268 patients, 352 lesions) and externally validated (150 patients, 204 lesions). The performance of the new score system was assessed by Harell's c-index. Using cutoff value of 12, maintaining positive predictive value ≥95%, the diagnostic performances of the score system were compared with those of LR-5.

Results: The 15-point diagnostic scoring system used MRI features (lesion size, nonrim arterial phase hyperenhancement, portal venous phase hypointensity, hepatobiliary phase hypointensity, and diffusion restriction) and clinical factors (alpha-fetoprotein and platelet). It showed good discrimination in the derivation (c-index, 0.946) and validation cohorts (c-index, 0.907). Using a risk score of 12 as a cut-off, this system yielded higher sensitivity than LR-5 (derivation cohort, 76.8% vs. 52.1%; validation cohort, 73.4% vs. 49.5%) without significant decrease in specificity (derivation cohort, 93.1% vs. 97.2%, P = 0.074; validation cohort, 91.7% vs. 96.1%, P = 0.299).

Data Conclusion: A new score system showed improved sensitivity in chronic hepatitis B patients compared to LI-RADS without significant compromise in specificity. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.27962DOI Listing
October 2021

Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study.

JHEP Rep 2021 Dec 8;3(6):100361. Epub 2021 Sep 8.

Department of Medicine and State Key Laboratory of Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong.

Background & Aims: Functional cure of chronic HBV infection (CHB) without life-long treatment requires the restoration of defective HBV-specific humoral and cellular immunity. Therapeutic vaccines based on the major structural and non-structural proteins have been tested in patients with CHB but have shown scarce immunogenicity. BRII-179, also known as VBI-2601, is a novel formulation comprised of all 3 HBV surface envelope proteins (Pre-S1, Pre-S2, and S). Safety, antiviral activity, and immunogenicity of BRII-179 admixed with co-adjuvant interferon (IFN)-α were assessed in patients with CHB.

Method: This randomized, open-label, controlled phase Ib/IIa study included 2 dose levels, 20 μg BRII-179 (Part 1, n = 25) and 40 μg BRII-179 (Part 2, n = 24). Patients, virally suppressed under nucleos(t)ide analogue (NA) therapy were randomized 1:2:2 into 3 cohorts in Part 1 and 1:1 into 2 cohorts in Part 2 to receive 4 monthly intramuscular injections of BRII-179 admixed with/without 3 MIU IFN-α. Antibody and cellular responses to HBsAg, as well as evolution of circulating HBsAg were monitored.

Results: Both 20 μg and 40 μg BRII-179 with/without IFN-α were well tolerated with no severe adverse events. BRII-179 induced anti-HBs responses in >30% patients in all treatment cohorts, however, moderate anti-Pre-S1 or anti-Pre-S2 antibody responses were only observed in patients receiving BRII-179 with IFN-α. BRII-179 also restored S-, Pre-S1-, Pre-S2-specific IFN-γ-producing T-cells in the majority of treated patients. Overall, no notable reduction of HBsAg was observed after BRII-179 treatment.

Conclusion: In patients with CHB under NA therapy, BRII-179 with/without IFN-α exhibited a good safety profile and induced HBV-specific B- and T-cell immune responses. These data support further clinical evaluation of BRII-179 in combination with other therapies.

Clinical Trial Number: ACTRN12619001210167.

Lay Summary: BRII-179 is a therapeutic vaccine designed to improve the immune response in patients with chronic hepatitis B. In this study, BRII-179 alone or with a low dose of interferon-α was safe, well tolerated, and induced enhanced HBV-specific antibody and T-cell responses in patients with chronic hepatitis B. However, BRII-179 treatment alone had minimal effect on patient's virological status. The potential of BRII-179 to achieve a functional cure in conjunction with other agents is being evaluated in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhepr.2021.100361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502773PMC
December 2021

An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B.

J Hepatol 2021 Oct 1. Epub 2021 Oct 1.

Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada.

Background & Aims: Several risk models were recently developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk.

Methods: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from four hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development.

Results: In the derivation cohort and the two validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good prediction performance [concordance index (c-index), 0.79]. This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index, 0.79 vs. 0.64-0.74; all P < 0.001) and Caucasian validation cohorts [c-index, 0.81 vs. 0.57-0.79; all P < 0.05 except modified PAGE-B (P = 0.22)]. A calibration plot showed a satisfactory calibration function. When the patients were grouped into four risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up.

Conclusions: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir.

Lay Summary: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.09.025DOI Listing
October 2021

Methodological challenges of performing meta-analyses to compare the risk of hepatocellular carcinoma between chronic hepatitis B treatments.

J Hepatol 2021 Sep 27. Epub 2021 Sep 27.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA. Electronic address:

Despite several recent meta-analyses on the topic, the comparative risk of hepatocellular carcinoma in patients with chronic hepatitis B (CHB) receiving entecavir (ETV) or tenofovir disoproxil fumarate (TDF) remains controversial. The controversy partly results from the arbitrary nature of significance levels leading to contradictory conclusions from very similar datasets. However, the use of observational data, which is prone to both within- and between-study heterogeneity of patient characteristics, also lends additional uncertainty. The asynchronous introduction of ETV and TDF in East Asia, where the majority of these studies have been conducted, further complicates analyses, as does the ensuing difference in follow-up time between ETV and TDF cohorts. Researchers conducting meta-analyses in this area must make many methodological decisions to mitigate bias but are ultimately limited to the methodologies of the included studies. It is therefore important for researchers, as well as the audience of published meta-analyses, to be aware of the quality of observational studies and meta-analyses in terms of patient characteristics, study design and statistical methodologies. In this review, we aim to help clinicians navigate the published meta-analyses on this topic and to provide researchers with recommendations for future work.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.09.017DOI Listing
September 2021

Inclusive Quantification Assay of Serum Des-γ-Carboxyprothrombin Proteoforms for Hepatocellular Carcinoma Surveillance by Targeted Mass Spectrometry.

Hepatol Commun 2021 10 12;5(10):1767-1783. Epub 2021 Jun 12.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.

Hepatocellular carcinoma (HCC) is a malignant cancer with one of the highest mortality rates. Des-γ-carboxyprothrombin (DCP) is an HCC serologic surveillance marker that can complement the low sensitivity of alpha-fetoprotein (AFP). DCP exists in the blood as a mixture of proteoforms from an impaired carboxylation process at glutamic acid (Glu) residues within the N-terminal domain. The heterogeneity of DCP may affect the accuracy of measurements because DCP levels are commonly determined using an immunoassay that relies on antibody reactivity to an epitope in the DCP molecule. In this study, we aimed to improve the DCP measurement assay by applying a mass spectrometry (MS)-based approach for a more inclusive quantification of various DCP proteoforms. We developed a multiple-reaction monitoring-MS (MRM-MS) assay to quantify multiple noncarboxylated peptides included in the various des-carboxylation states of DCP. We performed the MRM-MS assay in 300 patients and constructed a robust diagnostic model that simultaneously monitored three noncarboxylated peptides. The MS-based quantitative assay for DCP had reliable surveillance power, which was evident from the area under the receiver operating characteristic curve (AUROC) values of 0.874 and 0.844 for the training and test sets, respectively. It was equivalent to conventional antibody-based quantification, which had AUROC values at the optimal cutoff (40 mAU/mL) of 0.743 and 0.704 for the training and test sets, respectively. The surveillance performance of the MS-based DCP assay was validated using an independent validation set consisting of 318 patients from an external cohort, resulting in an AUROC value of 0.793. Conclusion: Due to cost effectiveness and high reproducibility, the quantitative DCP assay using the MRM-MS method is superior to antibody-based quantification and has equivalent performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485883PMC
October 2021

Multiple imputation analysis for propensity score matching with missing causes of failure: An application to hepatocellular carcinoma data.

Stat Methods Med Res 2021 Oct 1;30(10):2313-2328. Epub 2021 Sep 1.

Department of Preventive Medicine (Biostatistics), Feinberg School of Medicine, Northwestern University, USA.

Propensity score matching is widely used to determine the effects of treatments in observational studies. Competing risk survival data are common to medical research. However, there is a paucity of propensity score matching studies related to competing risk survival data with missing causes of failure. In this study, we provide guidelines for estimating the treatment effect on the cumulative incidence function when using propensity score matching on competing risk survival data with missing causes of failure. We examined the performances of different methods for imputing the data with missing causes. We then evaluated the gain from the missing cause imputation in an extensive simulation study and applied the proposed data imputation method to the data from a study on the risk of hepatocellular carcinoma in patients with chronic hepatitis B and chronic hepatitis C.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/09622802211037075DOI Listing
October 2021

Association of aspirin and statin use with the risk of liver cancer in chronic hepatitis B: A nationwide population-based study.

Liver Int 2021 11 17;41(11):2777-2785. Epub 2021 Jul 17.

Liver Center, Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background & Aims: Aspirin and statins have been suggested to prevent hepatocellular carcinoma (HCC). However, the combined effects of aspirin and statins on HCC risk in patients with chronic hepatitis B (CHB) are not clear.

Methods: A nationwide nested case-control study was performed with data from the National Health Insurance Service gathered between 2005 and 2015 in Korea. In a cohort of 538,135 treatment-naïve, non-cirrhotic patients with CHB, 6,539 HCC cases were matched to 26,156 controls and were analysed by conditional logistic regression. Separate historical cohort studies for each drug were analysed by time-dependent Cox regression as a sensitivity analysis.

Results: In the nested case-control study, statins (OR 0.34; 95% CI 0.32-0.37) and aspirin (OR 0.92; 95% CI 0.85-0.99) were significantly associated with a HCC risk reduction. However, dose-dependent risk reduction was observed only with statins. By sensitivity analysis in the historical cohorts, statin users (n = 244,455; HR 0.67; 95% CI 0.66-0.68) and aspirin users (n = 288,777; HR 0.81; 95% CI 0.80-0.82) had significantly lower HCC risk. In the drug-stratified analyses, statins were associated with significantly reduced risk of HCC regardless of aspirin, whereas aspirin did not show such associations.

Conclusions: In this nationwide population-based study of patients with CHB, statin use was consistently associated with a significant and dose-dependent reduction in HCC risk. In contrast, the association between aspirin use and HCC risk reduction was not dose-dependent and was suggested to be confounded by statins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15011DOI Listing
November 2021

Risk of Hepatitis B Virus Reactivation in Patients Treated With Immunotherapy for Anti-cancer Treatment.

Clin Gastroenterol Hepatol 2021 Jun 26. Epub 2021 Jun 26.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background & Aims: Hepatitis B virus (HBV) reactivation is a well-known complication in patients with chronic hepatitis B treated with cytotoxic chemotherapy. However, the risk of HBV reactivation through use of immune checkpoint inhibitors (ICIs) is not well understood. Therefore, we aimed to evaluate the risk of HBV reactivation and hepatic adverse events in patients with cancer receiving ICIs according to cancer type and virologic serology.

Methods: This historical cohort study included 3465 patients with cancer treated with ICIs between January 2015 and September 2020. The primary outcome was the occurrence of HBV reactivation, and the secondary outcome was presence of hepatic adverse events during ICI treatment.

Results: The mean patient age was 62.2 years, and 68.8% of patients were men. Of the 3465 eligible patients, 511 (14.7%) showed hepatitis B surface antigen (HBsAg) positivity. The incidence rates of HBV reactivation of the total patients, HBsAg-positive patients, and HBsAg-negative patients were 0.14% (5/3465), 1.0% (5/511), and 0.0% (0/2954), respectively. Among HBsAg-positive patients, HBV reactivation occurred at a rate of 0.5% (2/409) and 2.9% (3/102) in patients with and without hepatocellular carcinoma, respectively. The HBV reactivation rates were 0.4% (2/464) and 6.4% (3/47) in patients with and without antiviral prophylaxis, respectively. Grade 3-4 hepatitis occurred in 23 (4.5%) HBsAg-positive, and 218 (7.4%) HBsAg-negative patients. No HBV-related fatality occurred. Only 2 patients (0.4%) experienced HBsAg seroclearance after ICI treatment among HBsAg-positive patients.

Conclusions: In general, HBV reactivation was rarely observed in patients with antiviral prophylaxis while undergoing ICI treatment. However, HBV reactivation may occur in HBsAg-positive patients without antiviral prophylaxis or noncompliant with antiviral prophylaxis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.06.019DOI Listing
June 2021

Entecavir versus tenofovir in patients with chronic hepatitis B: Enemies or partners in the prevention of hepatocellular carcinoma.

Clin Mol Hepatol 2021 Jul 23;27(3):402-412. Epub 2021 Jun 23.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seou, Korea.

Over the past several decades, entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have remained the first-line antiviral agents in several international guidelines. These two antiviral agents have shown similar short to intermediateterm efficacy, including virologic, biochemical, serologic, and histologic responses. However, huge controversies regarding the antiviral efficacy of ETV and TDF in preventing the development of hepatocellular carcinoma (HCC) still exist. In this review, we summarized recent studies that compared the treatment efficacy of ETV and TDF in terms of HCC development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3350/cmh.2021.0179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273642PMC
July 2021

Efficacy and Safety of Glecaprevir/Pibrentasvir in Korean Patients with Chronic Hepatitis C: A Pooled Analysis of Five Phase II/III Trials.

Gut Liver 2021 11;15(6):895-903

Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.

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%) experienced 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5009/gnl20321DOI Listing
November 2021

Clinical Study of Single-Stranded Oligonucleotide RO7062931 in Healthy Volunteers and Patients With Chronic Hepatitis B.

Hepatology 2021 Oct 25;74(4):1795-1808. Epub 2021 Aug 25.

Roche Innovation Centre, Welwyn Garden City, United Kingdom.

Background And Aims: RO7062931 is an N-acetylgalactosamine (GalNAc)-conjugated single-stranded locked nucleic acid oligonucleotide complementary to HBV RNA. GalNAc conjugation targets the liver through the asialoglycoprotein receptor (ASGPR). This two-part phase 1 study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO7062931 in healthy volunteers and patients with chronic hepatitis B (CHB) who were virologically suppressed.

Approach And Results: Part 1 was a single ascending dose study in healthy volunteers randomized to receive a single RO7062931 dose (0.1-4.0 mg/kg), or placebo. Part 2 was a multiple ascending dose study in patients with CHB randomized to receive RO7062931 at 0.5, 1.5, or 3.0 mg/kg or placebo every month for a total of 2 doses (Part 2a) or RO7062931 at 3.0 mg/kg every 2 weeks, 3.0 mg/kg every week (QW), or 4.0 mg/kg QW or placebo for a total of 3-5 doses (Part 2b). Sixty healthy volunteers and 59 patients received RO7062931 or placebo. The majority of adverse events (AEs) reported were mild in intensity. Common AEs included self-limiting injection site reactions and influenza-like illness. Supradose-proportional increases in RO7062931 plasma exposure and urinary excretion occurred at doses ≥3.0 mg/kg. In patients with CHB, RO7062931 resulted in dose-dependent and time-dependent reduction in HBsAg versus placebo. The greatest HBsAg declines from baseline were achieved with the 3.0 mg/kg QW dose regimen (mean nadir ~0.5 log  IU/mL) independent of HBeAg status.

Conclusions: RO7062931 is safe and well tolerated at doses up to 4.0 mg/kg QW. Supradose-proportional exposure at doses of 3.0-4.0 mg/kg was indicative of partial saturation of the ASGPR-mediated liver uptake system. Dose-dependent declines in HBsAg demonstrated target engagement with RO7062931.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31920DOI Listing
October 2021

Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study.

Liver Cancer 2021 Apr 3;10(2):107-114. Epub 2021 Mar 3.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Introduction: Atezolizumab-bevacizumab is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the optimal sequence of therapy after disease progression on atezolizumab-bevacizumab is unclear.

Methods: This multinational, multicenter, and retrospective study assessed clinical outcomes of patients with advanced HCC who received subsequent systemic therapy after progression on atezolizumab-bevacizumab between July 2016 and April 2019.

Results: Among 71 patients treated with atezolizumab-bevacizumab, a total of 49 patients who received subsequent systemic therapy were included in this analysis; the median age was 60 years (range, 37-80) and 73.5% were male. All patients were classified as Child-Pugh A and Barcelona-Clinic Liver Cancer stage C. Multikinase inhibitors (MKIs), including sorafenib ( = 29), lenvatinib ( = 19), and cabozantinib ( = 1), were used as second-line therapy for all patients. The objective response rate and disease control rate were 6.1 and 63.3%, respectively, in all patients. With a median follow-up duration of 11.0 months, median progression-free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI] 1.8-4.9) and 14.7 months (95% CI 8.1-21.2) in all patients. Median PFS with lenvatinib was significantly longer than that with sorafenib (6.1 vs. 2.5 months; = 0.004), although there was no significant difference in median OS (16.6 vs. 11.2 months; = 0.347). Treatment-related adverse events (TRAEs) of any grade and grade 3 occurred in 42 (85.7) and 8 (16.3%) of patients. Common TRAEs included hand-foot syndrome ( = 26, 53.1%), fatigue ( = 14, 28.6%), hypertension ( = 14, 28.6%), and diarrhea ( = 12, 24.5%).

Conclusion: Second-line treatment with MKIs, mostly sorafenib and lenvatinib, showed comparable efficacy and manageable toxicities in patients with advanced HCC after disease progression on atezolizumab-bevacizumab.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000512781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077483PMC
April 2021

Kinetics of the neutrophil-lymphocyte ratio during PD-1 inhibition as a prognostic factor in advanced hepatocellular carcinoma.

Liver Int 2021 09 24;41(9):2189-2199. Epub 2021 May 24.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background And Aims: Programmed death 1 (PD-1) inhibitors have improved survival outcomes and produced durable responses in advanced hepatocellular carcinoma (HCC) for some patients. Here, we evaluated the relationship between the baseline and kinetics of the neutrophil-lymphocyte ratio (NLR) and clinical outcomes in nivolumab-treated HCC patients.

Methods: All consecutive HCC patients treated with nivolumab between July 2017 and June 2020 were screened for the eligibility. The NLRs were calculated before and at 2, 4 and 6 weeks after treatment. Survival outcomes were compared based on the baseline and kinetics of NLR. We additionally analysed the association of the baseline and dynamic changes in the NLR with hyperprogression (HPD).

Results: Among the 194 included cases, most patients were male (82.0%) and had a Child-Pugh Class A disease (70.6%). Patients with a baseline NLR ≥ 3 (hazard ratio [HR] 2.46; 95% CI 1.63-3.71) had a poorer overall survival than patients with baseline NLR < 3. During the treatment, the NLR increased rapidly in patients developing HPD, and only a ΔNLR at 4 weeks was predictive of HPD. The risk of HPD increased by 20% for every 20% increase in the ΔNLR at 4 weeks. Accordingly, an NLR increase at 4 weeks (HR 1.79; 95% CI 1.19-2.68) was associated with an increased risk of death, especially among patients with a baseline NLR ≥ 3.

Conclusions: The baseline and on-treatment kinetics for the NLR are effective prognostic indicators in nivolumab-treated patients with HCC. This may help to guide patient selection and on-treatment strategies for immunotherapies in advanced HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14932DOI Listing
September 2021

Tenofovir Alafenamide for Drug-Resistant Hepatitis B: A Randomized Trial for Switching From Tenofovir Disoproxil Fumarate.

Clin Gastroenterol Hepatol 2021 May 4. Epub 2021 May 4.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background & Aims: It remains unknown whether tenofovir alafenamide (TAF) could replace tenofovir disoproxil fumarate (TDF) in patients with drug-resistant hepatitis B virus (HBV).

Methods: In this multicenter randomized non-inferiority trial, 174 patients with HBV resistant to multiple drugs (lamivudine, entecavir, and/or adefovir) under TDF monotherapy for ≥96 weeks were randomized 1:1 to switch to TAF (n = 87) or continue TDF (n = 87) for 48 weeks. The primary endpoint was proportion of patients with HBV DNA <60 IU/mL at week 48.

Results: At baseline, 84 and 80 patients had HBV DNA <60 IU/mL in the TAF and TDF groups, respectively. At week 48, the proportion of patients with HBV DNA <60 IU/mL was 98.9% (86/87) in TAF group, showing non-inferiority to TDF group (97.7%, 85/87; difference, 1.1%; 95% confidence interval, -2.7% to 5.0%). Changes in median alanine aminotransferase at week 48 from baseline were statistically different between TAF and TDF groups (-3 IU/L vs +2 IU/L; P = .02). TAF group showed a statistically greater increase in bone mineral density at spine (+1.84% vs +0.08%; P = .01) and numerically higher increase in mean estimated glomerular filtration rate (+8.2% vs +4.5%; P = .06) compared with TDF group. Compared with TDF group, TAF group showed significantly greater increases in mean body weight (0.71 vs -0.37 kg; P = .01) and total, low-density lipoprotein, and high-density lipoprotein cholesterol levels (P < .001 for all) at week 48 from baseline.

Conclusions: TAF could be substituted for TDF in patients with multidrug-resistant HBV for improved bone and renal safety without a loss of efficacy. However, increases in body weight and cholesterol levels with TAF treatment would be a concern. ClinicalTrials.gov no.: NCT03241641.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.04.045DOI Listing
May 2021

Towards a New Horizon for Individualized Surveillance Tools in Hepatocellular Carcinoma.

Clin Gastroenterol Hepatol 2021 Apr 30. Epub 2021 Apr 30.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, The Republic of Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.04.041DOI Listing
April 2021

Tenofovir disoproxil fumarate on the risk of hepatocellular carcinoma in chronic hepatitis B patients with failure to preceding treatments: A nationwide cohort study.

J Viral Hepat 2021 08 11;28(8):1150-1159. Epub 2021 May 11.

Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea.

Tenofovir disoproxil fumarate (TDF) monotherapy is recommended for the treatment of chronic hepatitis B (CHB) patients who are refractory to other drugs. Yet, little data are available for the effectiveness of TDF monotherapy compared with TDF-based combination therapy on the risk of hepatocellular carcinoma (HCC) and death/transplantation. This nationwide population-based cohort study included 11,289 CHB patients who initiated TDF rescue therapy after failure of preceding treatments between 2012 and 2014 in Korea. The risks of HCC and death/transplantation were compared between TDF combotherapy (n = 2,499) and TDF monotherapy (n = 8,790) groups. The findings were validated in a hospital cohort of 1,163 CHB patients. In the nationwide cohort, during 44.2 months of overall treatment duration, 529 patients developed HCC and 190 died or received transplantation. In the 2,499 propensity score-matched pairs, compared with TDF combotherapy, TDF monotherapy showed no significantly different risks of HCC (1.11/100 person-year [PY] vs. 1.32/100 PY; HR 1.23, 95% CI 0.95-1.60, p = .12) and death/transplant (0.43/100 PY vs. 0.42/100 PY; HR 1.04, 95% CI 0.67-1.60, p = .87). However, in the 469 propensity score-matched pairs of cirrhosis subcohort, TDF monotherapy was associated with a higher risk of HCC than TDF combotherapy (HR 1.46, 95% CI 1.002-2.12, p = .049). In the validation hospital cohort, TDF monotherapy was not associated with significantly different risks of HCC and death/transplant in the entire cohort and cirrhosis subcohort. In CHB patients with failure to preceding treatments, TDF monotherapy showed no higher risks of HCC and death/transplantation compared with TDF combotherapy. However, the comparative effectiveness of rescue TDF monotherapy should be further clarified in cirrhotic patients since the findings were not consistent in the nationwide and hospital cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvh.13530DOI Listing
August 2021

Reply.

Clin Gastroenterol Hepatol 2021 Mar 31. Epub 2021 Mar 31.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.03.035DOI Listing
March 2021

International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma.

Gastroenterology 2021 Jun 9;160(7):2572-2584. Epub 2021 Mar 9.

Division of Liver Diseases and Hematology/Medical Oncology, Liver Cancer Program, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.01.233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169638PMC
June 2021

Safety, Pharmacokinetics, and Pharmacodynamics of the Oral TLR8 Agonist Selgantolimod in Chronic Hepatitis B.

Hepatology 2021 Oct 14;74(4):1737-1749. Epub 2021 Sep 14.

Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background And Aims: In patients with chronic hepatitis B (CHB) infection, activation of toll-like receptor 8 may induce antiviral immunity and drive functional cure. Selgantolimod, a toll-like receptor 8 agonist, was evaluated in patients with CHB who were virally suppressed on oral antiviral treatment or viremic and not on oral antiviral treatment.

Approach And Results: In this phase 1b study, patients were randomized 4:1 to receive either selgantolimod or placebo once weekly. Virally suppressed patients received either 1.5 mg (for 2 weeks) or 3 mg (for 2 weeks or 4 weeks). Viremic patients received 3 mg for 2 weeks. The primary endpoint was safety, as assessed by adverse events (AEs), laboratory abnormalities, and vital sign examination. Pharmacokinetic and pharmacodynamic parameters were assessed by plasma analysis. A total of 38 patients (28 virally suppressed, 10 viremic) were enrolled from six sites in Australia, New Zealand, and South Korea. Twenty patients (53%) experienced an AE and 32 (84%) had laboratory abnormalities, all of which were mild or moderate in severity. The most common AEs were headache (32%), nausea (24%), and dizziness (13%). With a half-life of 5 hours, no accumulation of selgantolimod was observed with multiple dosing. Selgantolimod induced transient dose-dependent increases in serum cytokines, including IL-12p40 and IL-1RA, which are important for the expansion and activity of multiple T- cell subsets and innate immunity.

Conclusion: Selgantolimod was safe and well-tolerated in virally suppressed and viremic patients with CHB and elicited cytokine responses consistent with target engagement. Further studies with longer durations of selgantolimod treatment are required to evaluate efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31795DOI Listing
October 2021

Letter: serum hepatitis B virus DNA and risk of hepatocellular carcinoma in patients with chronic hepatitis B-authors' reply.

Aliment Pharmacol Ther 2021 03;53(6):763

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16278DOI Listing
March 2021

Radiofrequency ablation versus stereotactic body radiation therapy for small (≤ 3 cm) hepatocellular carcinoma: A retrospective comparison analysis.

J Gastroenterol Hepatol 2021 Jul 5;36(7):1962-1970. Epub 2021 Mar 5.

Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background And Aim: We compared the clinical outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) in small (≤ 3 cm) hepatocellular carcinoma.

Methods: A total of 266 patients treated with RFA (n = 179) or SBRT (n = 87) were reviewed. Local control rates (LCRs), intrahepatic recurrence-free survival (IHRFS) rates, and overall survival (OS) rates were compared. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline characteristics between the two groups.

Results: The median follow-up period was 50.3 months, and treatment method (RFA vs SBRT) was not a significant prognostic factor for LCR, OS, and IHRFS in both multivariate and IPTW-adjusted analyses. The 4-year LCRs after RFA and SBRT were 92.7% and 95.0%, respectively. Perivascular location was a significant prognostic factor for LCR in the entire patients and in the RFA group, but not in the SBRT group. The 4-year OS rates in the RFA and SBRT groups were 78.1% and 64.1%, respectively (P = 0.012). After IPTW adjustment, the 4-year LCRs (90.6% vs 96.3%) and OS rates (71.8% vs 70.2%) were not significantly different between the two groups. The rate of grade ≥ 3 adverse events was 0.6% (n = 1) in the RFA group and 1.1% (n = 1) in the SBRT group.

Conclusions: The two treatment methods showed comparable outcomes in terms of LCR, OS rate, and IHRFS rate after IPTW adjustment. SBRT seems to be a viable alternative method for small hepatocellular carcinomas that are not suitable for RFA due to tumor location.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.15442DOI Listing
July 2021

Combined Hepatocellular-Cholangiocarcinoma: Magnetic Resonance Imaging Features and Prognosis According to Risk Factors for Hepatocellular Carcinoma.

J Magn Reson Imaging 2021 06 9;53(6):1803-1812. Epub 2021 Feb 9.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) can develop in patients with and without risk factors for hepatocellular carcinoma (HCC).

Purpose: To compare the clinical and magnetic resonance imaging (MRI) characteristics of cHCC-CCA in patients with and without risk factors for HCC, and to assess the influence of risk factors on patient prognosis.

Study Type: Retrospective.

Population: A total of 152 patients with surgically confirmed cHCC-CCA.

Field Strength/sequence: 1.5-T and 3-T/T1-weighted dual gradient-echo in- and opposed-phase, T2-weighted turbo-spin-echo, diffusion-weighted single-shot spin-echo echo-planar, and T1-weighted three-dimensional gradient-echo contrast-enhanced sequences.

Assessment: MRI features according to the Liver Imaging Reporting and Data System (LI-RADS) and pathologic findings based on revised classification were compared between patients with and without risk factors for HCC. Overall survival (OS) and recurrence-free survival (RFS) were also compared between the two groups, and factors associated with survival were evaluated.

Statistical Tests: The clinico-pathologic and MRI features of the two groups were compared using Student's t-tests, Mann-Whitney U-tests, and chi-square tests. OS and RFS were evaluated by the Kaplan-Meier method, and factors associated with survival were evaluated by Cox proportional hazard model.

Results: cHCC-CCA in patients with risk factors were more frequently classified as LI-RADS category 4 or 5 (LR-4/5; probably or definitely HCC) (48.7%), whereas those without risk factors were more frequently classified as category M (LR-M; probably malignant, not specific for HCC) (63.6%). RFS and OS did not differ significantly according to risk factors (P = 0.63 and 0.83). Multivariable analysis showed that pathologic tumor type (hazard ratio 2.02; P < 0.05) and LI-RADS category (hazard ratio 2.19; P < 0.05) were significantly associated with RFS and OS, respectively.

Data Conclusion: Although MRI features of cHCC-CCA differed significantly between patients with and without risk factors for HCC, postsurgical prognosis did not. LI-RADS category and pathologic tumor type were independently correlated with postsurgical prognosis in patients with cHCC-CCA.

Level Of Evidence: 3 TECHNICAL EFFICACY STAGE: 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.27528DOI Listing
June 2021

Clinical outcomes of systemic therapy in patients with unresectable or metastatic combined hepatocellular-cholangiocarcinoma.

Liver Int 2021 06 11;41(6):1398-1408. Epub 2021 Mar 11.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background & Aims: The optimal systemic chemotherapy for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) has not yet been defined. The definition and classification of cHCC-CCA has changed recently in the 5th edition of WHO classification. We reviewed the pathological findings with the new classification and analysed the efficacy of systemic chemotherapy in patients with unresectable/metastatic cHCC-CCA.

Methods: Among 254 patients with histologically confirmed cHCC-CCA from 1999 to 2015 in Asan Medical Center, Seoul, Korea, 99 patients who received systemic chemotherapy for unresectable/metastatic disease were included. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were retrospectively evaluated.

Results: Sorafenib (n = 62) and cytotoxic chemotherapy (n = 37) were administered as first-line chemotherapies; the ORR was 14.1%, and the median PFS and OS were 3.8 and 10.6 months, respectively, with a median follow-up duration of 39.6 months. The efficacy outcomes were not significantly different between patients who received sorafenib and those who received cytotoxic chemotherapy (ORR, 9.7% vs 21.6%, P = .14; median PFS, 4.2 vs 2.9 months, P = .52; median OS, 10.7 vs 10.6 months, P = .34). In multivariate analysis, large intrahepatic tumour burden (≥30% of liver volume), elevated serum bilirubin and non-platinum containing first-line chemotherapy remained as significant prognostic factors for poorer OS.

Conclusions: The efficacy outcomes according to first-line treatment were not significantly different between sorafenib and cytotoxic chemotherapy, and pathological findings were not found to help for determining appropriate therapeutic agent or assessing the prognosis. To overcome the poor treatment outcomes, further studies are needed to find proper treatment targets, biomarkers and the best treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14813DOI Listing
June 2021

One-year Fibrosis-4 index helps identify minimal HCC risk in non-cirrhotic chronic hepatitis B patients with antiviral treatment.

Hepatol Int 2021 Feb 5;15(1):105-113. Epub 2021 Feb 5.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te St, Taipei, 10002, Taiwan.

Background And Aims: Fibrosis-4 (FIB-4) index is a HCC predictor in chronic hepatitis B (CHB) patients. However, little is known about whether FIB-4 helps identify non-cirrhotic CHB patients with minimal HCC risk after prolonged nucleos(t)ide analogue (NA) therapy.

Methods: A total of 1936 ethnically diverse, non-cirrhotic CHB patients were enrolled in this retrospective multi-national study. All patients received prolonged NA treatment, including entecavir and tenofovir disoproxil fumarate. We explored whether FIB-4 cutoff of 1.30, a marker indicative of mild fibrosis severity, could stratify HCC risks in these patients.

Results: A total of 48 patients developed HCC after a mean follow-up of 6.98 years. FIB-4 level at 1 year after treatment (1-year FIB-4) was shown to be associated with HCC development and was superior to pre-treatment FIB-4 value. When patients were stratified by 1-year FIB-4 of 1.30, the high FIB-4 group was at an increased HCC risk compared to the low FIB-4 group, with a hazard ratio of 4.87 (95% confidence interval: 2.48-9.55). Multivariable analysis showed that sex and 1-year FIB-4 were independent predictors, with none of the 314 female patients with low 1-year FIB-4 developing HCC. Finally, 1-year FIB-4 of 1.30 consistently stratified HCC risks in patients with low PAGE-B score, a score composed of baseline age, sex and platelet count, and the annual incidence rate of HCC was 0.11% in those with PAGE-B < 10 + 1-year FIB-4 < 1.30.

Conclusions: In non-cirrhotic CHB patients receiving prolonged NA therapy, 1-year FIB-4 < 1.30 is useful for identifying those with minimal HCC risk by combining with female sex or low PAGE-B score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-020-10124-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863859PMC
February 2021

Secondary prevention of hepatitis B virus-related hepatocellular carcinoma with current antiviral therapies.

Kaohsiung J Med Sci 2021 Apr 27;37(4):262-267. Epub 2021 Jan 27.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Over the past decades, marked advancement has been made in the prevention and treatment of hepatitis B virus (HBV) infection. Due to highly effective antiviral therapies for chronic hepatitis B (CHB), long-term clinical outcomes in patients with CHB has also been dramatically improved. However, current antiviral therapies for CHB cannot completely abolish the risk of hepatocellular carcinoma (HCC). In addition, current treatment guidelines for CHB should be interpreted with caution given that HBV-associated hepatocarcinogenesis could be underway in patients who are not eligible for antiviral therapies by current guidelines. Therefore, efforts to reconcile treatment guidelines with recent clinical evidence should be made for reducing further development of HCC. In this article, we review the secondary prevention of HBV-related HCC with current antiviral therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/kjm2.12364DOI Listing
April 2021

Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial.

Clin Mol Hepatol 2021 Apr 25;27(2):346-359. Epub 2021 Jan 25.

Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

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.

Conclusion: 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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3350/cmh.2020.0307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046633PMC
April 2021
-->