Hepatic Steatosis but Not Fibrosis Is Independently Associated with Poor Outcomes in Patients with Inflammatory Bowel Disease

Background/Aims@#Increased prevalence of nonalcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) has been reported. However, the effects of NAFLD on the outcome of IBD remains unclear. We investigated whether the presence of NAFLD could influence the outcomes of patients with IBD. @*Methods@#We recruited 3,356 eligible patients with IBD into our study between November 2005and November 2020. Hepatic steatosis and fibrosis were diagnosed using hepatic steatosisindex of ≥30 and fibrosis-4 of ≥1.45, respectively. The primary outcome was clinical relapse, defined based on the following: IBD-related admission, surgery, or first use of corticosteroids, immunomodulators, or biologic agents for IBD. @*Results@#The prevalence of NAFLD in patients with IBD was 16.7%. Patients with hepatic ste-atosis and advanced fibrosis were older, had a higher body mass index, and were more likely to have diabetes (all p<0.05). @*Conclusions@#Hepatic steatosis was independently associated with increased risks of clinical relapse in patients with ulcerative colitis and Crohn’s disease, whereas fibrotic burden in the liver was not. Future studies should investigate whether assessment and therapeutic intervention for NAFLD will improve the clinical outcomes of patients with IBD.

Diagnostic Pitfall and Clinical Characteristics of Variant Versus Wild-Type Transthyretin Amyloid Cardiomyopathy in Asian Population: The Korean Nationwide Cohort Study

Background@#Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes.We sought to characterize the clinical characteristics of ATTR-CM in Asia. @*Methods@#Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). @*Results@#Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010–2013 vs. 22 [21.0%] during 2014–2017 vs. 75 [71.4%] during 2018–2021).Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010–2013 to 77% between 2018–2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan.Asp38Ala was the most common mutation. @*Conclusion@#A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.

Factors associated with follow-up loss of suicide attempted patients by emergency department-based case management services

Objective@#Emergency department-based interventions are known to be effective at reducing the risk of repeat suicide attempts among patients admitted to emergency departments after attempting suicide. However, the factors that influence loss to follow-up after emergency department-based interventions are not well known. @*Methods@#This study investigated suicide attempt patients who registered with an emergency department-based intervention and received counseling at least once from January 2019 to December 2020. Patients were allocated to a follow-up group or a loss-to-follow-up group depending on whether emergency department-based interventions had been performed more than three times. Clinical factors and socioeconomic status were considered independent variables. Logistic regression analysis was performed to identify factors that influenced loss to emergency department-based interventions. @*Results@#Of 339 patients enrolled, 210 (61.9%) were lost to follow-up. Time taken to initiation of intervention after discharge (adjusted odds ratio [aOR]=2.42; 95% confidence interval [CI], 1.38-4.30) and suicide attempt associated with physical illness (aOR=0.31; 95% CI, 0.14-0.68) independently influenced loss to emergency department-based interventions. @*Conclusion@#Initiation of intervention after discharge significantly influenced emergency department-based intervention follow-up loss of suicide attempt patients. The study suggests initiation of intervention prior to discharge might reduce the risk of repeat suicide attempts.

Rectal metastasis arising from breast cancer: a case report

Breast cancer is the most common cancer among women worldwide. Breast cancer often metastasizes to the regional lymph nodes, bone, brain, liver, and lungs, whereas gastrointestinal tract metastases are rare. Herein, we present a rare case of rectal metastasis from breast cancer that occurred during palliative chemotherapy. A 69-year-old female with a history of invasive ductal carcinoma, negative for hormonal receptors and positive for human epidermal growth factor receptor 2 (HER2) receptor, underwent various treatments, including neoadjuvant chemotherapy, breast-conserving surgery, and adjuvant therapy. Eight months postoperatively, the patient experienced axillary lymph node recurrence, requiring palliative chemotherapy. Despite ongoing treatment, metastatic lesions were confirmed in the lungs and pleura. During palliative chemotherapy, the patient developed anal pain, and subsequent examination revealed an infiltrating rectal lesion. Despite histological confirmation of metastatic breast carcinoma and tubular adenoma, a multidisciplinary decision was made regarding palliative chemotherapy over surgical intervention. Eribulin was administered, but due to the patient’s inability to tolerate the treatment, she passed away 3 months after rectal lesion diagnosis. Although breast cancer metastasis to the rectum is rare, clinicians should consider the possibility of rectal involvement and perform a digital rectal examination if anal symptoms are present.

Comparison between Nivolumab and Regorafenib as Second-line Systemic Therapies after Sorafenib Failure in Patients with Hepatocellular Carcinoma

Purpose@#Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. @*Materials and Methods@#We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. @*Results@#Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). @*Conclusion@#Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.

Computed tomographic features of focal lipogranulomatous lymphangitis for differentiating from malignant intestinal lesions in a dog

An eight-year-old Maltese dog presented with diarrhea and anorexia. Ultrasonography revealed marked focal wall thickening with loss of layering in the distal ileum. Contrast-enhanced computed tomography (CT) revealed a preserved wall layer with hypoattenuating middle wall thickening. In some segments of the lesion, small nodules protruding toward the mesentery from the outer layer were observed. Histopathology revealed focal lipogranulomatous lymphangitis (FLL) with lymphangiectasia. This is the first report to describe the CT features of FLL in a dog. CT features of preserved wall layers with hypoattenuating middle wall thickening and small nodules can assist in diagnosing FLL in dogs.

Nuclear Factor Erythroid 2-Related Factor 2/Kelch-Like ECH-Associated Protein 1 as a Predictor of Prognosis and Radiotherapy Resistance in Patients With Locally Advanced Rectal Cancer: A Prospective Analysis

Background@#The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/ Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC). @*Methods@#In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed. @*Results@#The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity. @*Conclusion@#CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance.The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.

Loss of Neutralizing Activity of Tixagevimab/Cilgavimab (Evusheld™) Against Omicron BN.1, a Dominant Circulating Strain Following BA.5During the Seventh Domestic Outbreak in Korea in Early 2023

Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/ cilgavimab administration and the average PRNT ND 50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND 50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND 50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.

Risk of Hepatitis C Virus Transmission through Acupuncture: A Systematic Review and Meta-Analysis / 대한소화기학회지

Background/Aims@#Chronic hepatitis C is a major risk factor for liver cirrhosis, hepatocellular carcinoma, and hepatic failure. Although traditional practices, including acupuncture, tend to increase the risk of HCV infection, the association remains controversial. Therefore, the current meta-analytical study was undertaken to evaluate the risks of acupuncture and hepatitis C transmission. @*Methods@#Two researchers independently screened studies from the databases encompassing the period from inception to May 12, 2022. Baseline demographics, HCV transmission OR, and 95% CIs were extracted, pooled, and analyzed using random-effect models.Subgroup analyses utilizing study design and ethnicity were performed. Heterogeneity and publication bias were analyzed using the Higgins I2 test and funnel plots, respectively. @*Results@#In all, 28 studies with 194,826 participants (178,583 controls [91.7%] vs. 16,243 acupuncture users [8.3%]) were included in the final analysis. The pooled analysis showed that acupuncture users had a significantly higher HCV transmission rate than controls with heterogeneity (OR, 1.84 [1.46–2.32]; p<0.001; I2 =80%). In the subgroup analysis, both cross-sectional case-control (n=14; OR, 1.96 [1.47–2.61]; p<0.001; I2 =88%) and cross-sectional studies (n=12; OR, 1.85 [1.32–2.61]; p<0.001; I2 =0%) showed significantly higher HCV infection rates in the acupuncture group than in the control group. Both Asian and non-Asian acupuncture users showed a higher HCV transmission risk than the controls (all Ps <0.001). No significant publication bias was observed. @*Conclusions@#Our findings indicate that acupuncture increases the risk of HCV transmission. Due to HCV's contagiousness, unsafe medical and social practices (including acupuncture) should be performed with caution.

The Effect of Model for End-Stage Liver Disease 3.0on Disparities between Patients with and without Hepatocellular Carcinoma in Korea

Purpose@#The model for end-stage liver disease (MELD) 3.0 has recently been suggested for determining liver allocation. We aimed to apply MELD 3.0 to a Korean population and to discover differences between patients with and without hepatocellular carcinoma (HCC). @*Materials and Methods@#This study is a retrospective study of 2203 patients diagnosed with liver cirrhosis at Severance Hospital between 2016–2022. Harrell’s concordance index was used to validate the ability of MELD scores to predict 90-day survival. @*Results@#During a mean follow-up of 12.9 months, 90-day survival was 61.9% in all patients, 50.4% in the HCC patients, and 74.8% in the non-HCC patients. Within the HCC patients, the concordance index for patients on the waitlist was 0.653 using MELD, which increased to 0.753 using MELD 3.0. Among waitlisted patients, the 90-day survival of HCC patients was worse than that of non-HCC patients with MELD scores of 31–37 only (69.7% vs. 30.0%, p=0.001). Applying MELD 3.0, the 90-day survival of HCC patients was worse than that of non-HCC patients across a wider range of MELD 3.0 scores, compared to MELD, with MELD 3.0 scores of 21–30 and 31–37 (82.0% vs. 72.5% and 72.3% vs. 24.3%, p=0.02 and p<0.001, respectively). @*Conclusion@#MELD 3.0 predicted 90-day survival of the HCC patients more accurately than original MELD score; however, the disparity between HCC and non-HCC patients increased, particularly in patients with MELD scores of 21–30. Therefore, a novel exception score is needed or the current exception score system should be modified.

Inflammatory bowel disease–associated intestinal fibrosis

Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.

Cases of Pernio-Like Lesions after mRNA-1273 Vaccination with Clinical and Pathological Features: A Single-Center Experience

The currently available coronavirus disease 2019 (COVID-19) vaccines in South Korea include mRNA (Moderna® and Pfizer®) and adenoviral vector (AstraZeneca® and Janssen® ) vaccines. Dermatologic side effects of COVID-19 vaccines range from local injection site reactions to systemic eruptions, including morbilliform rashes or erythema multiforme. Pernio-like lesions, one of the most common cutaneous manifestations of COVID-19, have been rarely reported post-vaccination. Herein, we report four cases of pernio-like lesions, which were detected in a single tertiary hospital within 2 months, after the first dose of mRNA-1273 (Moderna® ) vaccination was administered. In this study, we discuss the clinical and pathological features of our cases and compare them with those of previously reported cases of pernio-like lesions after COVID-19 vaccination. It is pivotal to realize that perniolike lesions can be a possible side effect of COVID-19 vaccination and that the number of patients experiencing this side effect is bound to be quite high in real-world clinical settings.

Cardiovascular Risk Is Elevated in Lean Subjects with Nonalcoholic Fatty Liver Disease

Background/Aims@#Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear. @*Methods@#Data from the 2008 to 2011 Korea National Health and Nutrition Examination Surveysdatabase were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥–0.640. ASCVD risk was evaluated using the American College of Cardiol-ogy/American Heart Association guidelines. @*Results@#The frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p<0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio, 2.60 vs 1.93; p=0.023). @*Conclusions@#Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high risk for ASCVD than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.

Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer

Background@#Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT). @*Methods@#A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens. @*Results@#We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression. @*Conclusions@#This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas

Background@#Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features. @*Methods@#A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays. @*Results@#PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression. @*Conclusions@#PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases

The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.

Immunogenicity and Reactogenicity of Ad26.COV2.S in Korean Adults: A Prospective Cohort Study

Background@#As the coronavirus disease 2019 (COVID-19) pandemic continues, there are concerns regarding waning immunity and the emergence of viral variants. The immunogenicity of Ad26.COV2.S against wild-type (WT) and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated.Method: This prospective cohort study was conducted between June 2021 and January 2022 at two university hospitals in South Korea. Healthy adults who were scheduled to be vaccinated with Ad26.COV2.S were enrolled in this study. The main outcomes included anti-spike (S) IgG antibody and neutralizing antibody responses, S-specific T-cell responses (interferon-γ enzyme-linked immunospot assay), solicited adverse events (AEs), and serious AEs. @*Results@#Fifty participants aged ≥ 19 years were included in the study. Geometric mean titers (GMTs) of anti-S IgG were 0.4 U/mL at baseline, 5.2 ± 3.0 U/mL at 3–4 weeks, 55.7 ± 2.4 U/mL at 5–8 weeks, and 81.3 ± 2.5 U/mL at 10–12 weeks after vaccination. GMTs of 50% neutralizing dilution (ND50) against WT SARS-CoV-2 were 164.6 ± 4.6 at 3-4 weeks, 313.9 ± 3.6 at 5–8 weeks, and 124.4 ± 2.6 at 10–12 weeks after vaccination. As for the S-specific T-cell responses, the median number of spot-forming units/10 6 peripheral blood mononuclear cell was 25.0 (5.0–29.2) at baseline, 60.0 (23.3–178.3) at 5-8 weeks, and 35.0 (13.3–71.7) at 10–12 weeks after vaccination. Compared to WT SARS-CoV-2, ND50 against Delta and Omicron variants was attenuated by 3.6-fold and 8.2-fold, respectively. The most frequent AE was injection site pain (82%), followed by myalgia (80%), fatigue (70%), and fever (50%). Most AEs were grade 1–2, and resolved within two days. @*Conclusion@#Single-dose Ad26.COV2.S was safe and immunogenic. NAb titer and S-specific T-cell immunity peak at 5–8 weeks and rather decrease at 10–12 weeks after vaccination.Cross-reactive neutralizing activity against the Omicron variant was negligible.

Cost-effectiveness of chronic hepatitis C screening and treatment

Hepatitis C virus (HCV) infection is the second most common cause of chronic liver disease in South Korea, with a prevalence ranging from 0.6% to 0.8%, and HCV infection incidence increases with age. The anti-HCV antibody test, which is cheaper than the HCV RNA assay, is widely used to screen for HCV infections; however, the underdiagnosis of HCV is a major barrier to the elimination of HCV infections. Although several risk factors have been associated with HCV infections, including intravenous drug use, blood transfusions, and hemodialysis, most patients with HCV infections present with no identifiable risk factors. Universal screening for HCV in adults has been suggested to improve the detection of HCV infections. We reviewed the cost-effectiveness of HCV screening and the methodologies used to perform screening. Recent studies have suggested that universal HCV screening and treatment using direct-acting antivirals represent cost-effective approaches to the prevention and treatment of HCV infection. However, the optimal timing and frequency of HCV screening remain unclear, and further studies are necessary to determine the best approaches for the elimination of HCV infections.

Negligible risks of hepatocellular carcinoma during biomarker-defined immune-tolerant phase for patients with chronic hepatitis B

Background/Aims@#The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT. @*Methods@#Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA >20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of <1.45 were classified into the IT-group. The cumulative probability of HCC was estimated using Kaplan-Meier analysis. All patients were assessed until HCC development (intention-to-treat [ITT] analysis), whereas those suspected of experiencing CHB phase switch were assessed using the per-protocol (PP) and censored at the time of phase switch. @*Results@#The cumulative probability of HCC at 1-, 3-, and 5-years among the IT-group was zero, compared to AVT-treated patients with FIB-4 indices <1.45 during the same period: 0.2%, 0.6%, and 1.4%, respectively (P=0.264 for ITT and P=0.533 for PP). Among the initially screened 125 untreated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to the IT-group (P=0.005). Furthermore, among AVT-treated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to their counterpart (P<0.001). @*Conclusions@#The risk of HCC was negligible in the IT-group stringently defined by a low FIB-4 index. However, given that a higher HCC risk exists among untreated patients with higher FIB-4, appropriate criteria for AVT should be established.

Serum fibrosis index-based risk score predicts hepatocellular carcinoma in untreated patients with chronic hepatitis B

Background/Aims@#Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients. @*Methods@#Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort. @*Results@#180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted. @*Conclusion@#A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.