Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (COVID-19), there are lack of effective and proven treatments for end-stage renal disease (ESRD). The present study aims to evaluate the effectiveness of regdanvimab on mortality in COVID-19–infected patients on hemodialysis (HD). Methods: We conducted an observational retrospective study in 230 COVID-19–infected patients on HD, of whom 77 (33.5%) were administered regdanvimab alone or in combination with dexamethasone or remdesivir during hospitalization (regdanvimab group) and 153 patients (66.5%) were not (no regdanvimab group). The primary outcome was in-hospital mortality. We compared mortality rates according to the use of regdanvimab and investigated the factors associated with mortality. Results: Fifty-nine deaths occurred during hospitalization, 49 in the no regdanvimab group (32.0%) and 10 in the regdanvimab group (13.0%), and the mortality rate was significantly higher in the no regdanvimab group than that in the regdanvimab group (p = 0.001). Multivariate Cox regression analysis showed that malignancy (p = 0.001), SPO2 of <95% at admission (p = 0.003), and administration of antibiotics and regdanvimab (p = 0.007 and p = 0.002, respectively) were significantly associated factors with mortality. Conclusion: Regdanvimab administration is beneficial in improving prognosis in hospitalized COVID-19 patients on HD. Considering the vulnerability to infection and high mortality of ESRD patients, regdanvimab may be considered as a therapeutic option in COVID-19 patients on HD.

Background: /Aim: Immune checkpoint proteins regulating T-cell mediated anti-tumor immunity have been reported to affect clinical outcomes in multiple malignancies. This study aimed to investigate the prognostic effect of histological expression of immune checkpoint proteins in patients with resected hepatocellular carcinoma (HCC). Methods: A total of 221 patients with HCC who underwent curative resection were included. Expression of programmed-cell death ligand-1 (PD-L1) in tumor cells (tPD-L1) and tumor infiltrating mononuclear cells (TIMCs) (iPD-L1), programmed-cell death-1 in TIMCs (iPD-1), and cytotoxic T lymphocyte antigen-4 in TIMCs (iCTLA-4) were measured immunohistochemically. Results: Histo-positivity for iCTLA-4, iPD-1, iPD-L1, and tPD-L1 was 32.1%, 42.5%, 35.3%, and 14.9%, respectively. Multivariate logistic analyses revealed that male sex and tumor >5 cm were variables related to iCTLA-4 positivity (odds ratio [OR], 0.46 and 1.94, respectively; P<0.05). Poor differentiation was related to PD-L1 expression in both tumor cells and TIMCs (OR, 2.88 and 3.46, respectively; P<0.05). Microvascular invasion was significantly associated only with iPD-L1 (OR, 2.24; P<0.05). In time-dependent outcome analyses, expression of immune checkpoint proteins in TIMCs (i.e., iCTLA-4, iPD-1, and iPD-L1) was significantly related to longer overall survival and non-cancer-related survival (all P<0.05), but not to time-to-recurrence or cancer-specific deaths. Concurrent activation of the PD-1:PD-L1 and CTLA-4 pathways predicted improved outcomes in terms of overall survival and non-cancer related survival (P=0.06 and P=0.03, respectively). Conclusions Immune checkpoint proteins upregulated in TIMCs in HCC tissues have individual and additive effects in prolonging the survival of patients, specifically in terms of survival not related to cancer recurrence.

Hemodialysis (HD) patients are more vulnerable to viral epidemics, experiencing higher mortality rates compared to individuals without chronic kidney disease (CKD). This retrospective cohort study sought to demonstrate clinical outcomes and associated factors among coronavirus disease 2019 (COVID-19) confirmed Korean HD patients. Methods: From February 2020 to November 2021, the COVID-19 Task Force Team collected clinical data for HD patients with confirmed COVID-19 via a self-report survey of nephrologists. The composite outcome included in-hospital mortality, admission to the intensive care unit (ICU), and use of mechanical ventilation. Risk factors associated with clinical outcomes were analyzed among HD patients and compared to those of individuals without CKD using the COVID-19 database from the Korea Disease Control and Prevention Agency. Results: A total of 380 HD patients from 206 facilities were diagnosed with COVID-19. Fever (49.5%) and cough (25.7%) were the two most common initial symptoms. The overall in-hospital fatality rate was 22.4% and even higher among ICU admission cases (64.7%). Non-survivors were older, more frequently developed shortness of breath, and were more likely to come from a nursing hospital. Compared to the age- and sex-matched non-CKD population, HD patients showed greater risk of in-hospital mortality (hazard ratio, 2.07; 95% confidence interval, 1.56–2.75; p < 0.001) and composite outcome (hazard ratio, 3.50; 95% confidence interval, 2.56–4.77; p < 0.001). Conclusion: HD patients have a greater risk of in-hospital mortality and morbidity from COVID-19. Special attention should be paid to COVID-19 HD patients when they are older or present with symptoms.

Purpose: Contrast media is one of the most common cause of adverse drug reaction (ADR) in adult. However, there was little data reported about differences in ADR ratio and severity among iodinated contrast media (ICM). Methods: Medical records of 627,049 patients who performed computed tomography scan using low-osmolar nonionic iodinated contrast media from January 2015 to December 2018 were retrospectively reviewed. A total of 6 ICMs including iomeprol, iohexol, iopromide, iobitridol, ioversol, and iopamidol were used in this period. The incidence of ADR was compared to their total usage and dosage between each contrast media. Results: The incidence of ADR of iopromide (1.36%) and iomeprol (1.27%) was the highest when compared with the average incidence of 1% of 6 ICMs. Ioversol (0.67%), iohexol, and iobitridol (0.74%) had the lower incidence of ADR. The order of results adjusted by actual administered dosage, the use of premedication, and the prior exposure history of ICMs was similar. The fraction of moderate and severe ADR in overall ADR was slightly different, but not proportional to the incidence of ADR. Conclusion The incidence of ADR among 6 low-osmolar nonionic ICMs was significantly different when compared by the total number of usage and the total volume of dose. The incidence of ADR varied by nearly 2-fold depending on ICMs. Further study might need to explore the reason for the difference of incidence.

The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.

Background: Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis. Methods: Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses (‘not-NASH,’ ‘borderline,’ and ‘NASH’) of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system. Results: Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52–0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH. Conclusions A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

BACKGROUND: Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients. METHODS: Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting. RESULTS: Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest. CONCLUSIONS: Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.
Activating Transcription Factor 4 ; Apoptosis ; Autophagy ; Blotting, Western ; Carcinoma, Hepatocellular ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Death ; Cell Line ; Cell Survival ; DNA ; Drug Discovery ; Drug Repositioning ; Endoplasmic Reticulum ; Guanabenz ; Humans ; Mass Screening ; Peptide Initiation Factors ; Phosphorylation ; Primary Cell Culture

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive liver diseases that present as neonatal cholestasis. Little is known of this disease in Korea. METHODS: The records of five patients histologically diagnosed with PFIC, one with PFIC1 and four with PFIC2, by liver biopsy or transplant were reviewed, and ATP8B1 and ABCB11 mutation status was analyzed by direct DNA sequencing. Clinicopathological characteristics were correlated with genetic mutations. RESULTS: The first symptom in all patients was jaundice. Histologically, lobular cholestasis with bile plugs was the main finding in all patients, whereas diffuse or periportal cholestasis was identified only in patients with PFIC2. Giant cells and ballooning of hepatocytes were observed in three and three patients with PFIC2, respectively, but not in the patient with PFIC1. Immunostaining showed total loss of bile salt export pump in two patients with PFIC2 and focal loss in two. Lobular and portal based fibrosis were more advanced in PFIC2 than in PFIC1. ATP8B1 and ABCB11 mutations were identified in one PFIC1 and two PFIC2 patients, respectively. One PFIC1 and three PFIC2 patients underwent liver transplantation (LT). At age 7 months, one PFIC2 patient was diagnosed with concurrent hepatocellular carcinoma and infantile hemangioma in an explanted liver. The patient with PFIC1 developed steatohepatitis after LT. One patient showed recurrence of PFIC2 after 10 years and underwent LT. CONCLUSIONS: PFIC is not rare in patients with neonatal cholestasis of unknown origin. Proper clinicopathologic correlation and genetic testing can enable early detection and management.
Bile ; Biopsy ; Carcinoma, Hepatocellular ; Cholestasis ; Cholestasis, Intrahepatic ; Fatty Liver ; Fibrosis ; Genetic Testing ; Giant Cells ; Hemangioma ; Hepatocytes ; Humans ; Jaundice ; Korea ; Liver ; Liver Diseases ; Liver Transplantation ; Recurrence ; Sequence Analysis, DNA

Biliary adenofibroma is a rare tumor with a bile duct origin characterized by a complex tubulocystic non-mucin secreting biliary epithelium with abundant fibrous stroma. The MRI features of biliary adenofibroma are not well established. The authors encountered two patients with biliary adenofibroma and reviewed the literature focusing on the MRI findings. A well-circumscribed multicystic tumor with septal enhancement and no intrahepatic bile duct communication may be the characteristic MRI findings of biliary adenofibroma.
Adenofibroma ; Bile Ducts ; Bile Ducts, Intrahepatic ; Epithelium ; Humans ; Magnetic Resonance Imaging

Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.
Adenoma, Liver Cell ; Bone Marrow ; Carcinoma, Hepatocellular ; Female ; Humans ; Liver ; Metaplasia ; Ultrasonography ; Young Adult