Tailored hydration with lactated Ringer's solution for post-endoscopic retrograde cholangiopancreatography pancreatitis prevention: A randomized controlled trial.

OBJECTIVES: Aggressive hydration using lactated Ringer's solution (LRS) prevents post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Concerns of this strategy are large volume and lengthy hydration. Our study aimed to evaluate the efficacy of tailored aggressive hydration (TAH) for PEP prevention. METHODS: In this prospective, multicenter, double-blinded, randomized trial conducted across three tertiary Korean hospitals, patients who underwent ERCP for the first-time were randomly assigned (1:1) to tailored standard hydration (TSH) and TAH groups. The TSH group received 1.5 mL/kg/h LRS during and after ERCP, whereas the TAH group was administered a 20 mL/kg bolus post-ERCP and 3 mL/kg/h during and after the procedure. Both groups were assessed for elevated serum amylase levels and pain 4-6 h after ERCP. If both were absent, hydration was discontinued. If either was present, hydration was continued at the original rate until 8 h. The primary endpoint was PEP development and was analyzed on an intention-to-treat analysis. RESULTS: A total of 344 patients were randomly assigned to treatment groups (171 to the TSH group and 172 to the TAH group). PEP was observed in 9.4% (16/171) in the TSH group and 3.5% (6/172) in the TAH group (relative risk 0.37, 95% confidence interval 0.15-0.93, p = 0.03). No difference was identified between the two groups in terms of PEP severity (p = 0.80) and complications related to volume overload (p = 0.32). CONCLUSIONS: TAH according to the presence of abdominal pain or elevated serum amylase levels at 4-6 h after ERCP is safe and prevents PEP development.

Prognosis of Patients with Chronic Hepatitis C Genotype 1b Infection Treated Using Daclatasvir/Asunaprevir after Sustained Virologic Response: A 6-Year Multicenter Prospective Observational Study.

Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5-60.0] months; median age: 58 [49-67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child-Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.

A double layer agar plate method results in an improvement for enumerating Vibrio vulnificus and Vibrio parahaemolyticus exposed to nutrient deficiency and refrigeration temperature.

This study sought to І)investigate the effect of varying concentrations of salt on the survival of Gram-negative bacteria in artificial seawater (ASW; pH 6) stored at 4 °C, ІІ)examine the culturable populations of Vibrio vulnificus persisting in ASW with or without 1000 U/mg catalase or 0.1% sodium pyruvate (pH 6) under aerobic and oxygen-restricted environments at 4 °C, and ІІІ)determine whether double layer agar plate (DLAP) methods can improve the culturability of V. vulnificus and Vibrio parahaemolyticus in ASW (pH 6) stored at 4 °C. Once incubated in ASW containing 10% salt at 4 °C, Escherichia coli O157:H7, Salmonella Typhimurium, and Shigella flexneri survived at levels over at least 3.42-4.65 log CFU/mL on day 28, but V. vulnificus underwent the inability to produce colonies within 7 days, while maintaining its membrane integrity. A positive correlation between sodium pyruvate and maintenance of platable colony-forming capability was observed in V. vulnificus incubated aerobically. Using tryptic soy agar containing 3% salt (TSAS) overlayed by thiosulfate-citrate-bile salts-sucrose agar (TCBS), a higher platable colony count of Vibrio spp. was recovered from ASW after 25 or 30 days of storage at 4 °C, followed by TSAS, TSAS overlayed by marine agar (MA), MA, and TCBS.

Changing Trends in Liver Cirrhosis Etiology and Severity in Korea: the Increasing Impact of Alcohol.

BACKGROUND: Chronic hepatitis B is the most common cause of liver cirrhosis in South Korea. However, alcoholic liver disease has shown an increasing trend. Although the clinical implications surrounding liver cirrhosis have been changing over the years, few studies have recently examined cirrhosis epidemiology. Therefore, we aimed to investigate changes in liver cirrhosis etiology and severity in Korea. METHODS: We retrospectively reviewed 16,888 records of cirrhotic patients from six tertiary hospitals in Korea from 2008 to 2017. Continuous and non-continuous variables were processed via linear and Poisson regression, expressed as beta (B) coefficients and as exponentiated values of coefficients (Exp[B]), respectively. RESULTS: Chronic hepatitis B showed a decreasing trend (Exp[B] = 0.975, P < 0.001), whereas alcohol showed an increasing trend (Exp[B] = 1.013, P = 0.003), occupying the most common etiology in 2017. The Child-Turcotte-Pugh (CTP) score and decompensated liver cirrhosis prevalence did not change over the 10-year period. The incidence of variceal bleeding, severe ascites, hepatic encephalopathy, and spontaneous bacterial peritonitis significantly decreased from 12.3% to 7.7%, 7.8% to 4.1%, 1.0% to 0.5%, and 1.9% to 1.1%, respectively (P < 0.05 for all). In the subgroup analysis, the chronic hepatitis B group showed improving CTP scores (B = -0.025, P < 0.001) and decreasing decompensated liver cirrhosis rates (Exp[B] = 0.977, P = 0.016), whereas the alcohol group demonstrated increasing CTP class C (Exp[B] = 1.031, P = 0.005) and model for end-stage liver disease scores (B = 0.081, P = 0.005) over 10 years. CONCLUSION: The chronic hepatitis B group exhibited improved results, whereas the alcohol group still presented poor liver functions and outcomes. Future national policies and systematic approaches addressing the incidence, prevention, and treatment of alcoholic liver cirrhosis are indispensable.

Characteristics of viable-but-nonculturable Vibrio parahaemolyticus induced by nutrient-deficiency at cold temperature.

Vibrio parahaemolyticus has been consistently found to be involved in the food-borne disease outbreaks every year. Particularly, V. parahaemolyticus can be induced into a viable but nonculturable (VBNC) state under cold-starvation conditions. In this physiological state, V. parahaemolyticus losses its colony-forming ability and shows reduced metabolic activities. The subsequent failure of its detection may threaten public health-hygiene practices. Until now, evident information on physiological properties of VBNC V. parahaemolyticus and its underlying mechanism remains unclear and unorganized. Therefore, this review summarized survival behavior, persistence, and entry of pathogenic microorganisms into a VBNC state in response to various environmental conditions and discussed distinctive characteristics of VBNC cells. To survive under unfavorable environments, VBNC V. parahaemolyticus shows marked modifications in cell membrane composition, fatty acid synthesis, morphology, metabolism, gene expression, and capability of adhesion and virulence. These physiological modifications might be closely associated with an imbalance in maintaining essential biological processes within VBNC cells, thereby causing a decrease in cell membrane fluidity. To develop an efficient surveillance method and to prevent the recovery of VBNC cells in food, the induction of a VBNC state needs to be profoundly understood.

Sphingobium tyrosinilyticum sp. nov., a tyrosine hydrolyzing bacterium isolated from Korean radish garden.

A yellow-pigmented novel bacterial strain, MAH-12T, was isolated from a soil sample of Korean radish garden and was characterized using a polyphasic approach. Cells were Gram-staining negative, non-motile and rod-shaped. The strain was aerobic, catalase positive, optimum growth temperature and pH were 28-30 °C and 6.0, respectively. The novel strain is able to hydrolyze L-tyrosine, starch, esculin and 4-nitrophenyl-ß-D-galactopyranoside. On the basis of 16S rRNA gene sequence analysis, strain MAH-12T belongs to the genus Sphingobium and is most closely related to several Sphingobium type strains (97.2-97.8%). In DNA-DNA hybridization tests, the DNA relatedness between strain MAH-12T and its closest phylogenetic neighbors was below 45.0%. The DNA G + C content was 64.0 mol% and the predominant respiratory quinone was ubiquinone-10. The major cellular fatty acids were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) and C16:0. The DNA-DNA hybridization results and results of the genotypic analysis in combination with chemotaxonomic and physiological data demonstrated that strain MAH-12T represented a novel species within the genus Sphingobium, for which the name Sphingobium tyrosinilyticum is proposed. The type strain is MAH-12T (= KACC 19297T = CGMCC 1.16225T). The NCBI GenBank accession number for the 16S rRNA gene sequence of strain MAH-12T is KY964278 and the digital protologue database taxon number of strain MAH-12T is TA00463.

Review: Comparison of the effectiveness of decontaminating strategies for fresh fruits and vegetables and related limitations.

Given that it should be aware of the nutritional benefits, resulting from the consumption of fresh fruits and vegetables consumed raw and/or minimally processed, comparing the efficacy of different individual sanitizing methods against the major food-borne pathogens localized in fresh commodities is of much importance; these products are easily vulnerable to the microbial contamination. In this review, the current propensity of alternative sanitizing methods was introduced, as well as principal elements for deteriorating the cleaning effects were also discussed. Chlorine-based-sanitizers exhibited the microbial reduction of <1.12 log10 CFU/g on fruits and vegetables. Most of aqueous disinfectants showed ≤3.01 log10-redcutions against a variety of microorganisms inoculated on fresh commodities. Similarly, several physical technologies such as hydrostatic pressure and ultraviolet light were effective for reducing surviving bacterial cells could recover and grow rapidly during the whole processing, posing a potential risk of causing food-borne outbreaks associated with the fresh products. The invasion and subsequent localization of the organisms into the inner parts of products, interactions between the microbial cell and food-contacting surfaces, as well as development of biofilms could restrict the antimicrobial activity of the currently used approaches.

CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation.

CXXC5 is a member of a small subset of proteins containing CXXC-type zinc-finger domain. Here, we show that CXXC5 is a transcription factor activating Flk-1, a receptor for vascular endothelial growth factor. CXXC5 and Flk-1 were accumulated in nucli and membrane of mouse embryonic stem cells (mESCs), respectively, during their endothelial differentiation. CXXC5 overexpression induced Flk-1 transcription in both endothelium-differentiated mESCs and human umbilical vein endothelial cells (HUVECs). In vitro DNA binding assay showed direct interaction of CXXC5 on the Flk-1 promoter region, and mutation on its DNA-binding motif abolished transcriptional activity. We showed that bone morphorgenetic protein 4 (BMP4) induced CXXC5 transcription in the cells, and inhibitors of BMP signaling suppressed the CXXC5 induction and the consequent Flk-1 induction by BMP4 treatment. CXXC5 knockdown resulted in suppression of BMP4-induced stress fiber formation (56.8 ± 1.3% decrease, P<0.05) and migration (54.6 ± 1.9% decrease, P<0.05) in HUVECs. The in vivo roles of CXXC5 in BMP-signaling-specific vascular development and angiogenesis were shown by specific defect of caudal vein plex vessel formation (57.9 ± 11.8% decrease, P<0.05) in cxxc5 morpholino-injected zebrafish embryos and by suppression of BMP4-induced angiogenesis in subcutaneously injected Matrigel plugs in CXXC5(-/-) mice. Overall, CXXC5 is a transcriptional activator for Flk-1, mediating BMP signaling for differentiation and migration of endothelial cell and vessel formation.

Correction to: Toxigenic diversity of Bacillus cereus isolated from fresh produce and effects of various factors on the growth and the cytotoxicity of B. cereus.

[This corrects the article DOI: 10.1007/s10068-023-01330-0.].

Toxigenic diversity of Bacillus cereus isolated from fresh produce and effects of various factors on the growth and the cytotoxicity of B. cereus.

This study analyzed the virulence, growth characteristics, and cytotoxicity of Bacillus cereus strains isolated from fresh produce, including romaine lettuce, sesame leaf, tomato, and cucumber grown by different methods. Polymerase chain reaction (PCR) was used to assess the toxigenic potential, and the cytotoxicity of B. cereus was estimated using cell-free supernatant in HEp-2 cells. The study found that hblD was the predominant diarrheal enterotoxin in the 59 isolated B. cereus strains, followed by nheB and hblC. The optimal temperatures for growth ranged from 42 to 44 °C, with the highest growth rates and shortest lag times. Cytotoxicity varied greatly depending on abiotic factors, including NaCl, pH, and medium, and was not always correlated with cell population. The study highlights the importance of establishing control measures to prevent B. cereus intoxication in fresh vegetables. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01330-0.

Impact of Prospero Homeobox-1 (PROX-1) οn the Oncogenic Phenotypes of Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells. MATERIALS AND METHODS: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting. RESULTS: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and forkhead box O1 (FOXO1) in HCC cells. After PROX-1 knockdown, their phosphorylation was reversed. CONCLUSION: PROX-1 overexpression is associated with the invasive and oncogenic phenotypes of human HCC cells via GSK-3ß and FOXO1 phosphorylation.

Management of early-stage hepatocellular carcinoma: challenges and strategies for optimal outcomes.

Although hepatocellular carcinoma (HCC) is associated with a poor prognosis, management of early-stage HCC is often successful with highly efficacious treatment modalities such as liver transplantation, surgical resection, and radiofrequency ablation. However, unfavorable clinical outcomes have been observed under certain circumstances, even after efficient treatment. Factors that predict unsuitable results after treatment include tumor markers, inflammatory markers, imaging findings reflecting tumor biology, specific outcome indicators for each treatment modality, liver functional reserve, and the technical feasibility of the treatment modalities. Various strategies may overcome these challenges, including the application of reinforced treatment indication criteria with predictive markers reflecting tumor biology, compensation for technical issues with up-to-date technologies, modification of treatment modalities, downstaging with locoregional therapies (such as transarterial chemotherapy or radiotherapy), and recently introduced combination immunotherapies. In this review, we discuss the challenges to achieving optimal outcomes in the management of early-stage HCC and suggest strategies to overcome these obstacles.

Development of a selective medium for the enumeration of lactic acid bacteria and bifidobacteria in food products.

This study was conducted to develop a selective medium for enumerating LAB and Bifidobacteria in food samples. Thirteen media were evaluated to determine their suitability for selectively enumerating LAB (17 bacilli and 7 cocci) and Bifidobacteria (12 strains) under aerobic and anaerobic conditions. When BL, BCP, and mMRS were supplemented with propionic acid (5 ml/l) and adjusted to pH 5, the growth of all indicator microorganisms was inhibited; however, these media also inhibited the growth of certain LAB and Bifidobacterial strains. Using propionic acid, the pH levels of BL, BCP, and mMRS were adjusted to pH 5.2, 6.0, and 6.0, respectively. These media inhibited the growth of all indicator microorganisms, whereas they did not inhibit any of the LAB and Bifidobacteria strains under anaerobic conditions. Overall, BLP (pH 5.8) lacking blood showed significantly higher bacterial counts compared with other media in food products. Further analyses indicated that BLP (pH 5.8) was the most suitable medium for enumerating LAB and Bifidobacteria in food. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01202-z.

Acute respiratory distress syndrome and severe pneumonitis after atezolizumab plus bevacizumab for hepatocellular carcinoma treatment: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a high mortality. However, the treatment options for advanced HCC are limited to tyrosine kinase inhibitors, such as sorafenib and lenvatinib. Since previous regimens have an insufficient efficacy, the combination therapy of atezolizumab and bevacizumab (Ate/Bev) has been investigated, which showed an improvement in progression-free and overall survival. However, the adverse events of this combination therapy in advanced HCC have not been established. Herein, we report a novel case of an unresectable HCC and acute respiratory distress syndrome (ARDS) after a combination therapy of Ate/Bev. CASE SUMMARY: An 82-year-old male visited our outpatient clinic for an incidentally detected liver mass. Liver magnetic resonance imaging and enhanced chest computed tomography (CT) were performed, which showed arterial hyperenhancement with washout in delayed phase suggesting HCC, and a well-defined metastatic solid nodule, respectively. F-18 fluorodeoxyglucose positron emission tomography (PET)-CT exhibited multiple hypermetabolic lesions in the iliac bone, lumbar vertebrae, and femur. Because of the high burden of the intrahepatic tumor, transarterial radioembolization was initially performed; after 37 d, a combination therapy of Ate/Bev was administered. The patient visited the emergency department three days after Ate/Bev treatment complaining of dyspnea. He was diagnosed with severe pneumonitis based on CT. Despite administering oxygen via a high-flow nasal cannula, the P/F ratio was only 74; therefore, the patient was diagnosed with ARDS based on the overall examination results. Low tidal volume with high positive end-expiratory pressure, sedative agents combined with a neuromuscular blocker, and a systemic steroid were promptly applied to manage the ARDS. However, the patient did not recover from the hypoxia and expired 31 h after being admitted. CONCLUSION: Clinicians should be aware of severe pneumonitis due to the immune-related adverse events of this combination therapy, and patients should be closely monitored after therapy.

First Case of Atypical, Generalized Skin Rash after Transarterial Chemoembolization in a Patient with Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) is a widely used hepatocellular carcinoma (HCC) treatment. Some cases of supraumbilical skin rash after TACE in patients with HCC have been reported. To the best of the authors' knowledge, there are no reports on atypical, generalized rashes caused by doxorubicin systemic absorption after TACE. This paper presents the case of a 64-year-old male with HCC who developed generalized macules and patches one day after a successful TACE procedure. A histology examination of a skin biopsy of a dark reddish patch on the knee revealed severe interface dermatitis. He was treated with a topical steroid, and all skin rashes improved within a week with no side effects. This report presents this rare case with a literature review on skin rash after TACE.

Altered Frequency, Activation, and Clinical Relevance of Circulating Innate and Innate-Like Lymphocytes in Patients With Alcoholic Liver Cirrhosis.

Alcoholic liver cirrhosis (ALC) is caused by chronic alcohol overconsumption and might be linked to dysregulated immune responses in the gut-liver axis. However, there is a lack of comprehensive research on levels and functions of innate lymphocytes including mucosal-associated invariant T (MAIT) cells, NKT cells, and NK (NK) cells in ALC patients. Thus, the aim of this study was to examine the levels and function of these cells, evaluate their clinical relevance, and explore their immunologic roles in the pathogenesis of ALC. Peripheral blood samples from ALC patients (n = 31) and healthy controls (HCs, n = 31) were collected. MAIT cells, NKT cells, NK cells, cytokines, CD69, PD-1, and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. Percentages and numbers of circulating MAIT cells, NKT cells, and NK cells were significantly reduced in ALC patients than in HCs. MAIT cell exhibited increased production of IL-17 and expression levels of CD69, PD-1, and LAG-3. NKT cells displayed decreased production of IFN-γ and IL-4. NK cells showed elevated CD69 expression. Absolute MAIT cell levels were positively correlated with lymphocyte count but negatively correlated with C-reactive protein. In addition, NKT cell levels were negatively correlated with hemoglobin levels. Furthermore, log-transformed absolute MAIT cell levels were negatively correlated with the Age, Bilirubin, INR, and Creatinine score. This study demonstrates that circulating MAIT cells, NKT cells, and NK cells are numerically deficient in ALC patients, and the degree of cytokine production and activation status also changed. Besides, some of their deficiencies are related to several clinical parameters. These findings provide important information about immune responses of ALC patients.

A Mixture of Morus alba and Angelica keiskei Leaf Extracts Improves Muscle Atrophy by Activating the PI3K/Akt/mTOR Signaling Pathway and Inhibiting FoxO3a In Vitro and In Vivo.

Muscle atrophy, which is defined as a decrease in muscle mass and strength, is caused by an imbalance between the anabolism and catabolism of muscle proteins. Thus, modulating the homeostasis between muscle protein synthesis and degradation represents an efficient treatment approach for this condition. In the present study, the protective effects against muscle atrophy of ethanol extracts of Morus alba L. (MA) and Angelica keiskei Koidz. (AK) leaves and their mixtures (MIX) were evaluated in vitro and in vivo. Our results showed that MIX increased 5-aminoimidazole-4-carboxamide ribonucleotide-induced C2C12 myotube thinning, and enhanced soleus and gastrocnemius muscle thickness compared to each extract alone in dexamethasone-induced muscle atrophy Sprague Dawley rats. In addition, although MA and AK substantially improved grip strength and histological changes for dexamethasone-induced muscle atrophy in vivo, the efficacy was superior in the MIX-treated group. Moreover, MIX further increased the expression levels of myogenic factors (MyoD and myogenin) and decreased the expression levels of E3 ubiquitin ligases (atrogin-1 and muscle-specific RING finger protein-1) in vitro and in vivo compared to the MA- and AK-alone treatment groups. Furthermore, MIX increased the levels of phosphorylated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) that were reduced by dexamethasone, and downregulated the expression of forkhead box O3 (FoxO3a) induced by dexamethasone. These results suggest that MIX has a protective effect against muscle atrophy by enhancing muscle protein anabolism through the activation of the PI3K/Akt/mTOR signaling pathway and attenuating catabolism through the inhibition of FoxO3a.

Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study.

This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

Amiodarone-Induced Multi-Systemic Toxicity Involving the Liver, Lungs, Thyroid, and Eyes: A Case Report.

Objectives: Amiodarone is widely used to treat arrhythmia. However, amiodarone is known for its severe toxicity to the liver, lungs, and thyroid. Amiodarone causes liver damage ranging from asymptomatic serum aminotransferase elevation to hepatic failure requiring liver transplantation. Although amiodarone toxicity has been reported, its simultaneous multi-organ toxicity is not well-known. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, lungs, thyroid, and eyes. Case Presentation: A 61-year-old woman visited the emergency room due to general weakness, nausea, visual disturbance, heat intolerance, and a non-productive cough. The patient had been using clopidogrel and amiodarone due to underlying atrial fibrillation. The total level of bilirubin was 0.71 mg/dL, aspartate aminotransferase was 358 U/L, alanine aminotransferase was 177 U/L, and prothrombin time was 27.1 s. Computed tomography showed diffuse increased liver intensity and scattered hyperattenuated nodular consolidations in both lungs. Transthoracic needle lung biopsy revealed fibrinoid interstitial inflammation with atypical change of type II pneumocytes and intra-alveolar foamy macrophages. In addition, the thyroid-stimulating hormone level was <0.008 µIU/mL, and free thyroxine was 4.67 ng/dL. The thyroid scan showed diffuse homogenous intake of technetium-99 m pertechnetate in both thyroid lobes. The ophthalmologic exam detected bilateral symmetrical corneal deposits in a vortex pattern. With these findings, we could diagnose amiodarone-induced hepatic, pulmonary, thyroid, and ophthalmologic toxicity. Liver function was restored after cessation of amiodarone, and thyroid function was normalized with methimazole administration. However, due to aggravated lung consolidations, systemic steroid treatment was administered, and improvement was seen 1 week after, at the follow-up exam. As her symptoms improved, she was discharged with a plan of steroid administration for 3 to 6 months. Conclusions: This case implies the possibility of multi-systemic amiodarone toxicity. Thus, the toxicity of amiodarone to multiple organs must be monitored. Prompt cessation of the drug should be considered upon diagnosis.