Publications by authors named "Da Woon Sim"

28 Publications

  • Page 1 of 1

Efficacy of add-on therapy with intravenous immunoglobulin in steroid hyporesponsive DRESS syndrome.

Clin Transl Sci 2021 Nov 18. Epub 2021 Nov 18.

Division of Allergy, Asthma, and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially life-threatening, delayed, drug-induced hypersensitivity reaction. Immediate withdrawal of the culprit drug and administration of systemic corticosteroids is the most widely accepted treatment. However, it is difficult to manage patients with DRESS syndrome who are not responsive to systemic steroids. We studied the efficacy of intravenous immunoglobulins (IVIGs) in patients with DRESS syndrome unresponsive to systemic steroids. We retrospectively reviewed patients with DRESS syndrome who received IVIG in addition to systemic steroids during 2012-2017 and compared the clinical features and course of DRESS syndrome, before and after IVIG treatment. Eighteen DRESS patients (9 men) were included. The most frequent offending drugs were dapsone in five patients, followed by vancomycin in three patients, and carbamazepine in three patients. Rash, fever, lymphadenopathy, atypical lymphocytes, and hepatic involvement were common clinical findings. IVIG treatment was added within a median time of 7 days from the commencement of systemic steroid therapy. After IVIG treatment (total dosage: 1-2 g/kg), the fever resolved within a median time of 1 day (range, 0-3) and liver enzymes improved substantially within a median time of 13 days (range, 0-27). No severe adverse reactions related to IVIG therapy were observed in this study; however, there was one case of mortality. The addition of IVIG in DRESS syndrome in cases refractory to systemic steroid treatment may be helpful in hastening recovery. However, comparative studies using a placebo group are needed.
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http://dx.doi.org/10.1111/cts.13201DOI Listing
November 2021

High occurrence of simultaneous multiple-drug hypersensitivity syndrome induced by first-line anti-tuberculosis drugs.

World Allergy Organ J 2021 Jul 28;14(7):100562. Epub 2021 Jul 28.

Department of Allergy and Clinical Immunology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, South Korea.

Background: Multiple drug hypersensitivity syndrome (MDHS) results in treatment delay or failure and often results in severe drug hypersensitivity reactions. There are few reports of MDHS in response to anti-tuberculosis drugs; however, clinical information is scarce. Understanding the frequency and clinical characteristics of simultaneous MDHS against first-line anti-tuberculosis drugs in patients with non-severe drug hypersensitivity reactions is necessary.

Methods: We reviewed 27 patients with drug fever or maculopapular exanthem in response to first-line anti-tuberculosis drugs between January 2010 and June 2019. Drug fever or maculopapular exanthem occurred when isoniazid, rifampin, ethambutol, and pyrazinamide were administered simultaneously. Drug provocation tests for the 4 drugs were performed to identify the culprit drugs.

Results: All patients showed positive reactions to 1 or more drugs. MDHS was diagnosed in 13 (48%) patients, of whom 11 and 2 patients reacted to 2 and 3 drugs, respectively. In comparison to the patients with single-drug hypersensitivity, the patients with MDHS did not exhibit any differences in characteristics. Ethambutol and rifampin were the common drugs that induced a reaction, and the combination of these 2 drugs induced MDHS most frequently. Among the patients with MDHS, there were no differences between the drugs that caused drug fever and maculopapular exanthem. All patients with MDHS were successfully treated with alternative drugs.

Conclusions: Simultaneous MDHS may occur frequently in patients with drug fever or maculopapular exanthem caused by first-line anti-tuberculosis drugs, indicating the need to evaluate the allergy responses for all 4 drugs, even in patients without severe drug hypersensitivity. The combination of ethambutol and rifampin was the most common trigger that induced MDHS.
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http://dx.doi.org/10.1016/j.waojou.2021.100562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339324PMC
July 2021

Fixed drug eruption and anaphylaxis induced concurrently by erdosteine: a case report.

Allergy Asthma Clin Immunol 2021 Feb 5;17(1):15. Epub 2021 Feb 5.

Division of Allergy, Asthma, and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School, 42 Jebong-ro, Dong-gu, Gwangju, 61469, Republic of Korea.

Background: Erdosteine is used as a mucolytic agent and has a low incidence of adverse drug reactions, most of which are gastrointestinal and mild. Moreover, drug antigens rarely induce multiple simultaneous immunologic reactions. Only one previous case report has demonstrated hypersensitivity reaction induced by erdosteine. Here, we report a case of fixed drug eruption and anaphylaxis, which were concurrently induced by erdosteine. The association between the symptoms and erdosteine was proven by a drug provocation test.

Case Presentation: A 35-year-old woman presented with recurrent angioedema and pruritic rash on the hands, which developed within 2 h following the administration of drugs, including erdosteine, for acute upper respiratory infection. Her rash was characterized by well-defined erythematous plaques, which recurred at the same site following the administration of the medications. She also experienced angioedema of the lips. Fixed drug eruption was considered after excluding other possible causes for the presented skin lesions. A drug provocation test confirmed that fixed drug eruption on both hands had occurred after administration of erdosteine, suggesting that erdosteine was the cause of the allergic reaction. However, she also experienced angioedema, isolated wheal, and laryngeal edema; thus, IgE-mediated type I hypersensitivity could also be concurrently occurring with the fixed drug eruption.

Conclusions: We report about a patient who was diagnosed with two different hypersensitivity reactions concurrently induced by erdosteine. We also demonstrate that patients may exhibit multiple simultaneous symptoms that usually arise from overlapping of different hypersensitivity mechanisms. Physicians should be aware of the possibility that some patients who are allergic to certain drugs could exhibit several symptoms caused by different mechanisms of hypersensitivity reactions simultaneously.
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http://dx.doi.org/10.1186/s13223-021-00517-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866636PMC
February 2021

A Nationwide Study of Severe Cutaneous Adverse Reactions Based on the Multicenter Registry in Korea.

J Allergy Clin Immunol Pract 2021 02 19;9(2):929-936.e7. Epub 2020 Sep 19.

Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea.

Background: Because severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) rarely occur, clinical data based on large-scale studies are still lacking.

Objective: To provide information on culprit drugs and clinical characteristics, including morbidity and mortality of SCARs based on a nationwide registry.

Methods: SCAR cases that occurred from 2010 to 2015 were recruited to the Korean SCAR registry from 34 tertiary referral hospitals. Demographics, causative drugs, causality, and clinical outcomes were collected by reviewing the medical record.

Results: A total of 745 SCAR cases (384 SJS/TEN cases and 361 DRESS cases) due to 149 drugs were registered. The main causative drugs were allopurinol (14.0%), carbamazepine (9.5%), vancomycin (4.7%), and antituberculous agents (6.3%). A strong preference for SJS/TEN was observed in carbonic anhydrase inhibitors (100%), nonsteroidal anti-inflammatory drugs (84%), and acetaminophen (83%), whereas dapsone (100%), antituberculous agents (81%), and glycopeptide antibacterials (78%) were more likely to cause DRESS. The mortality rate was 6.6% (SJS/TEN 8.9% and DRESS 4.2%). The median time to death was 19 days and 29 days in SJS/TEN and DRESS respectively, and 89.8% of deaths occurred within 60 days after the onset of the skin symptoms.

Conclusion: Allopurinol, carbamazepine, vancomycin, and antituberculous agents were the leading causes of SCARs in Korea. Some drugs preferentially caused a specific phenotype. The mortality rate of SCARs was 6.6%, and most of the deaths occurred within 2 months.
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http://dx.doi.org/10.1016/j.jaip.2020.09.011DOI Listing
February 2021

Effects of Air Purifiers on Patients with Allergic Rhinitis: a Multicenter, Randomized, Double-Blind, and Placebo-Controlled Study.

Yonsei Med J 2020 Aug;61(8):689-697

Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Exposure to particulate matter (PM) is a well-known risk factor in the triggering and exacerbation of allergic airway disease. Indoor environments, where people spend most of their time, are of utmost importance. To assess the effects of air purifiers [equipped with high-efficiency particulate air (HEPA) filters] on allergic rhinitis (AR) in adult patients, we performed a multicenter, randomized, double-blind, and placebo-controlled study.

Materials And Methods: Patients with house dust mite (HDM)-induced AR were randomly assigned to either active or mockup (placebo) air-purification groups. Two air purifiers (placed in living room and bedroom) were operated for 6 weeks in each home environment. The primary study endpoint was to achieve improvement in AR symptoms and medication scores. Secondary endpoints were to achieve improvement in the quality of life (QoL) and visual analog scale (VAS) scores, as well as in the indoor (bedroom and living room) concentrations of PM and PM.

Results: After 6 weeks of air purifier use, medication scores improved significantly in the active (vs. placebo) group, although subjective measures (symptoms, VAS, and QoL scores) did not differ. Bedroom PM concentrations initially exceeded living room or outdoor levels, but declined (by up to 51.8%) following active purifier operation. Concentrations of PM in living room and PM in bedroom and living room were also significantly reduced through active purification.

Conclusion: The use of air purifiers with HEPA filters significantly reduced medication requirements for patients with HDM-induced AR and significantly lowered indoor PM concentrations, regardless of room placement. Active intervention to reduce household air pollutants may help improve allergic airway disease (clinicaltrials.gov NCT03313453).
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http://dx.doi.org/10.3349/ymj.2020.61.8.689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393300PMC
August 2020

The first case of tegoprazan-induced urticaria.

J Clin Pharm Ther 2020 Oct 29;45(5):1187-1189. Epub 2020 Jun 29.

Division of Allergy, Asthma, and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.

What Is Known And Objective: Tegoprazan induces adverse drug reactions during clinical trials; however, tegoprazan-induced urticaria has not been reported. Here, we describe the first case of this.

Case Description: A 55-year-old woman presented with acute urticaria with pruritus after taking the gastro-oesophageal reflux disease medication, tegoprazan. Urticaria disappeared after tegoprazan discontinuation. In an oral provocation test, after taking 10% of tegoprazan, she developed pruritus, and after taking 30%, she developed urticaria on her back.

What Is New And Conclusion: This is the first case of urticaria induced by tegoprazan. Physicians should understand the possibility of a tegoprazan-induced hypersensitivity reactions.
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http://dx.doi.org/10.1111/jcpt.13150DOI Listing
October 2020

HLA-DRB1*15: 02 Is Associated With Iodinated Contrast Media-Related Anaphylaxis.

Invest Radiol 2020 05;55(5):304-309

Department of Internal Medicine, Chung-Ang University Hospital, Seoul, South Korea.

Background: The incidence of severe reaction induced by iodinated contrast media (ICM) has increased over the years with an increasing use of imaging modalities. Although ICM anaphylaxis is rare, it can be life-threatening, but currently, there is no biomarker that can identify individuals at risk of ICM anaphylaxis.

Objective: The aim of this study is to investigate the genetic susceptibility of ICM anaphylaxis.

Methods: Patients who had ICM anaphylaxis were enrolled in the study, and their blood samples were collected for genotyping of human leukocyte antigen (HLA)-A, -B, -C, and -DR. The results were compared with those of healthy Korean general population. MRGPRX2 gene in ICM anaphylaxis group was also sequenced and compared with the Korean standard database of genetic polymorphism.

Results: The frequencies of 3 HLA alleles (B*52:01, C*12:02, and DRB1*15:02) were significantly higher in 47 patients with ICM anaphylaxis. In particular, HLA-DRB1*15:02 was 5 times more frequent in the ICM anaphylaxis group than the Korean general population (34.0% vs 6.6%; odds ratio, 7.306; 95% confidence interval, 3.622-14.740), and this difference was most pronounced in subjects with iohexol-induced anaphylaxis (odds ratio, 16.516; 95% CI, 5.241-52.047; P < 0.0001). Eight single nucleotide polymorphisms were identified in MRGPRX2 gene, but their frequencies were not different in those with ICM anaphylaxis compared with the general Korean population.

Conclusions: HLA-DRB1*15:02 is associated with ICM anaphylaxis in the Korean population.
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http://dx.doi.org/10.1097/RLI.0000000000000644DOI Listing
May 2020

Variation of clinical manifestations according to culprit drugs in DRESS syndrome.

Pharmacoepidemiol Drug Saf 2019 06 1;28(6):840-848. Epub 2019 May 1.

Division of Allergy, Asthma and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.

Purpose: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but serious condition that systematically damages various internal organs through T-cell-mediated immunological drug reactions. We aimed to investigate whether clinical manifestations of DRESS syndrome differ according to culprit drugs.

Methods: We retrospectively analyzed data from 123 patients with probable/definite DRESS syndrome based on the RegiSCAR criteria (January 2011 to July 2016). The data were obtained from the Korean Severe Cutaneous Adverse Reaction Registry. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre criteria. The culprit drugs were categorized as allopurinol, carbamazepine, anti-tuberculosis drug, vancomycin, cephalosporins, dapsone, and nonsteroidal anti-inflammatory drugs.

Results: Differences were observed among culprit drugs regarding the frequencies of hepatitis (P < 0.01), renal dysfunction (P < 0.0001), lymphadenopathy (P < 0.01), and atypical lymphocyte (P < 0.01). Latency period differed among culprit drugs (P < 0.0001), being shorter in vancomycin and cephalosporin. In terms of clinical severity, admission duration (P < 0.01) and treatment duration (P < 0.05) differed among culprit drugs, being longer in vancomycin and anti-tuberculosis drugs, respectively.

Conclusions: Based on the findings, clinical manifestations, including latency period and clinical severity, may differ according to culprit drugs in DRESS syndrome.
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http://dx.doi.org/10.1002/pds.4774DOI Listing
June 2019

Differentiation of angioimmunoblastic T-cell lymphoma from DRESS syndrome.

J Allergy Clin Immunol Pract 2019 May - Jun;7(5):1684-1686.e1. Epub 2018 Dec 14.

Division of Allergy, Asthma, and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2018.11.048DOI Listing
August 2020

What Are the Clinical Features and Etiology of Eosinophilic Liver Infiltration?

Gut Liver 2019 03;13(2):183-190

Gastroenterology, Department of Internal Medicine, Gwangju, Korea.

Background/aims: Although eosinophilic liver infiltration (ELI) is not rare, few data exist regarding its clinical characteristics and etiology. Therefore, we evaluated these aspects to better understand the clinical implications of this lesion type, which is reasonably common in Korea.

Methods: Patients suspected of having ELI, based on abdominal computed tomography results obtained between January 2010 and September 2017, were enrolled in this retrospective study. The presumptive etiologies of ELI were categorized as parasite infections, hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), malignancies, and unidentified. Clinical courses and treatment responses were also evaluated.

Results: The mean age of the enrolled patients (male, 237/328) was 62 years. Most patients (63%) were diagnosed incidentally and had peripheral eosinophilia (90%). Only 38% of the enrolled patients (n=126) underwent further evaluations to elucidate the etiology of the suspected ELI; 82 (25%) had parasite infections, 31 (9%) had HES, five (2%) had EGPA, and five (2%) had drug reactions in conjunction with eosinophilia and systemic symptoms. Almost half of the other enrolled patients had cancer. Radiologic resolution was achieved in 191 patients (61%; median time to radiologic resolution, 185 days). Resolution of peripheral eosinophilia was achieved in 220 patients (79%). In most cases, the course of ELI was benign.

Conclusions: This large ELI study is unique in that the incidence rate, underlying diseases, and clinical courses were comprehensively evaluated. Clinicians should investigate the etiology of ELI, as several of the underlying diseases require intervention rather than observation.
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http://dx.doi.org/10.5009/gnl18266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430429PMC
March 2019

Complete response of hepatocellular carcinoma with right atrium and pulmonary metastases treated by combined treatments (a possible treatment effect of natural killer cell): A case report and literature review.

Medicine (Baltimore) 2018 Oct;97(42):e12866

Division of Gastroenterology.

Rationale: Hepatocellular carcinomas (HCCs) with metastases to the right atrium (RA) and lungs are rare, with a poor prognosis. Furthermore, the treatment outcomes in patients with advanced HCCs remain unsatisfactory.

Patient Concerns: A 46-year-old man presented to our hospital for dyspnea on exertion and abdominal pain.

Diagnoses: HCC and extra-hepatic metastases to the lung and RA.

Interventions: Multidisciplinary treatment including radiotherapy (RT), transarterial chemoembolization (TACE), and sorafenib. During a follow-up evaluation computed tomography, he experienced a radio-contrast-induced anaphylaxis. After the event, treatment such as RT, TACE, and sorafenib were continued.

Outcomes: His tumor burden decreased, finally leading to a complete response as per the modified Response Evaluation Criteria in Solid Tumors. The patient is still alive, 30 months after the episode. Subsequent blood tests showed increased natural killer (NK) cell activity, which was significantly higher than that seen in other age-matched HCC patients with an identical stage of the tumor, receiving sorafenib. This suggests that the increase in NK cells induced by anaphylaxis influenced the tumor burden.

Lessons: We report here a rare case of long-term survival of an HCC patient with multiple metastases treated with multidisciplinary modalities, in which high NK cell activity was observed after a radio-contrast-induced anaphylactic reaction during follow-up investigations.
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http://dx.doi.org/10.1097/MD.0000000000012866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211840PMC
October 2018

Unusual Clinical Manifestation of Laryngeal Edema in a Case of DRESS Syndrome.

J Allergy Clin Immunol Pract 2018 Nov - Dec;6(6):2108-2109. Epub 2018 Mar 21.

Division of Allergy, Asthma, and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju, Korea.

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http://dx.doi.org/10.1016/j.jaip.2018.03.001DOI Listing
November 2019

Comparison between Newly Developed and Commercial Inhalant Skin Prick Test Reagents Using In Vivo and In Vitro Methods.

J Korean Med Sci 2018 Mar 26;33(13):e101. Epub 2018 Mar 26.

Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: We developed skin prick test (SPT) reagents for common inhalant allergens that reflected the real exposure in Korea. The study aim was to evaluate diagnostic usefulness and allergen potency of our inhalant SPT reagents in comparison with commercial products.

Methods: We produced eight common inhalant allergen SPT reagents using total extract (Prolagen): Dermatophagoides farinae, Dermatophagoides pteronyssinus, oak, ragweed, mugwort, Humulus japonicus pollens, as well as cat and dog allergens. We compared the newly developed reagents with three commercially available SPT reagents (Allergopharma, Hollister-Stier, Lofarma). We measured total protein concentrations, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), major allergen concentration, and biological allergen potencies measured by immunoglobulin E (IgE) immunoblotting and ImmunoCAP inhibition test.

Results: Diagnostic values of these SPT reagents were expressed as positivity rate and concordance rate of the results from ImmunoCAP allergen-specific IgE test in 94 allergic patients. In vitro analysis showed marked differences in protein concentrations, SDS-PAGE features, major allergen concentrations, and biological allergen potencies of four different SPT reagents. In vivo analysis showed that positive rates and concordance rates of Prolagen® SPT reagents were similar compared to the three commercial SPT reagents.

Conclusion: The newly developed Prolagen® inhalant SPT reagents are not inferior to the commercially available SPT reagents in allergy diagnosis.
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http://dx.doi.org/10.3346/jkms.2018.33.e101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865053PMC
March 2018

A Case of Schnitzler's Syndrome without Monoclonal Gammopathy-Associated Chronic Urticaria Treated with Anakinra.

Yonsei Med J 2018 Jan;59(1):154-157

Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.

Chronic urticaria may often be associated with interleukin (IL)-1-mediated autoinflammatory disease, which should be suspected if systemic inflammation signs are present. Here, we report a case of Schnitzler's syndrome without monoclonal gammopathy treated successfully with the IL-1 receptor antagonist anakinra. A 69-year-old man suffered from a pruritic urticarial rash for 12 years. It became aggravated episodically and was accompanied by high fever, arthralgia, leukocytosis, and an elevated C-reactive protein and erythrocyte sedimentation rate. The episodes each lasted for over one week. Neutrophilic and eosinophilic inflammation was found on skin biopsy. However, serum and urine electrophoresis showed no evidence of monoclonal gammopathy. The cutaneous lesions were unresponsive to various kinds of anti-histamines, systemic glucocorticoids, colchicine, cyclosporine, dapsone, and methotrexate, which were administered over a span of 3 years immediately preceding successful treatment. A dramatic response, however, was observed after a daily administration of anakinra. This observation suggests that the correct diagnosis of this case is Schnitzler's syndrome without monoclonal gammopathy. For an adult patient with refractory chronic urticaria and systemic inflammation, Schnitzler's syndrome could be considered as a possible differential diagnosis. Although the typical form of Schnitzler's syndrome exhibits the presence of monoclonal gammopathy as a diagnostic criterion, monoclonal gammopathy may be absent in an atypical form. In such a situation, an IL-1 antagonist should be effective for the management of chronic urticaria.
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http://dx.doi.org/10.3349/ymj.2018.59.1.154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725354PMC
January 2018

Comparison of Singleplex Specific IgE Detection Immunoassays: ImmunoCAP Phadia 250 and Immulite 2000 3gAllergy.

Ann Lab Med 2018 Jan;38(1):23-31

Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: The identification of clinically meaningful specific immunoglobulin E (sIgE) is important for the diagnosis and management of allergic diseases. Various in vitro sIgE detection methods are available worldwide. Depending on the number of antigens that can be tested simultaneously, there are two representative methods: singleplex and multiplex. Singleplex sIgE detection is mainly provided by Thermo Fisher (ImmunoCAP) and Siemens (Immulite). This study aimed to compare the diagnostic agreement of two singleplex sIgE detection assays.

Methods: Sera from 209 Korean patients with allergic disease were used to compare the ImmunoCAP and Immulite assays with respect to the following allergens: inhalant allergens (Dermatophagoides farinae, cat and dog dander, oak, rye grass, mugwort, Alternaria, German cockroach) and food allergens (hen's egg white, cow's milk, wheat, peanut, soybean, and shrimp). Data from 902 paired comparison tests were included for comparisons. Qualitative, semi-quantitative, and quantitative comparisons were performed using statistical analyses.

Results: In qualitative comparisons, the positivity and negativity agreements ranged from 75% (wheat, shrimp) to 96% (Alternaria). Class consistency (classes 0-6) was well matched. Spearman's rank correlation coefficients for all allergens except shrimp were over 0.7. In quantitative comparisons, all allergens excluding shrimp showed >0.7 intra-class correlation coefficients.

Conclusions: The ImmunoCAP and Immulite systems showed similar performances. However, clinicians should consider fundamental methodological differences between the assays.
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http://dx.doi.org/10.3343/alm.2018.38.1.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700143PMC
January 2018

Characterization of a Major Allergen from Mongolian Oak, Quercus mongolica, a Dominant Species of Oak in Korea.

Int Arch Allergy Immunol 2017 25;174(2):77-85. Epub 2017 Oct 25.

Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.

Background: Oaks are the most common trees in Korean forests, and Mongolian oak, Quercus mongolica, is the dominant species. However, no allergen has been characterized from Mongolian oak. In this study, we tried to characterize a major allergen from Mongolian oak.

Methods: A molecule homologous to pathogenesis-related 10 (PR-10)-like protein, Que m 1, was cloned by RT-PCR. Its recombinant protein, along with Que a 1, an allergen from white oak (Q. alba), was produced. The allergenicity and diagnostic value of recombinant Que m 1, Que a 1, and Bet v 1 proteins were compared by ELISA using sera from oak-sensitized subjects. A basophil activation test was also performed using CD63 expression as an activation marker.

Results: Que m 1 sequence shares 57.5-96.2% amino acid sequence identity with PR-10-like allergens from various plants. Specific IgE to recombinant Que m 1, Que a 1, and Bet v 1 were detected in 92.0, 74.0, and 38.0% of 50 serum samples from Korean tree pollinosis patients. Recombinant Que m 1 was able to inhibit IgE reactivity to Que a 1 and Bet v 1, indicating its strong cross-reactivity. The activation patterns of basophils from 5 patients were similar in terms of the CD63 expression and protein concentration of challenged Bet v 1 and Que m 1.

Conclusions: A major allergen, Que m 1, was cloned, and its recombinant protein was produced from Mongolian oak, a dominant species in Korea. Recombinant Que m 1 is potentially useful for the diagnosis and treatment of tree pollinosis in Korea.
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http://dx.doi.org/10.1159/000481092DOI Listing
December 2017

Comparison of the ImmunoCAP Assay and AdvanSure™ AlloScreen Advanced Multiplex Specific IgE Detection Assay.

Yonsei Med J 2017 Jul;58(4):786-792

Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: The AdvanSure™ AlloScreen assay is an advanced multiplex test that allows for simultaneous detection of specific IgE (sIgE) against multiple allergens. For precise identification of causative allergens in allergic patients, we compared this new multiplex sIgE assay with the ImmunoCAP assay, which is currently the gold-standard method for sIgE detection.

Materials And Methods: Serum samples from 218 Korean allergic disease patients were used to compare the ImmunoCAP and AlloScreen assays with respect to the following 13 allergens: Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat and dog dander, Alternaria, birch, oak, ragweed, mugwort, rye grass, and food allergens (egg white, cow's milk, peanuts).

Results: A total of 957 paired tests using the 13 allergens were compared. The total agreement ratio ranged from 0.74 (oak) to 0.97 (Alternaria). With respect to class association analyses, the gamma index ranged from 0.819 (rye grass) to 0.990 (Alternaria). The intra-class correlation coefficients for house dust mites, cat and dog dander, Alternaria, birch, ragweed, egg white, cow's milk, and peanut sIgE titers were >0.8.

Conclusion: The AlloScreen and ImmunoCAP assays exhibited similar diagnostic performance. However, due to methodological differences between the two systems, careful interpretation of their results is needed in clinical applications.
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http://dx.doi.org/10.3349/ymj.2017.58.4.786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447110PMC
July 2017

Accurate assessment of alpha-gal syndrome using cetuximab and bovine thyroglobulin-specific IgE.

Mol Nutr Food Res 2017 10 3;61(10). Epub 2017 Jul 3.

Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.

Scope: IgE against galactose-α-1,3-galactose (α-Gal) causes alpha-gal syndrome. Bovine thyroglobulin (BTG) and cetuximab share this epitope. We aimed to determine the utility of specific IgE (sIgE) against cetuximab as compared to BTG for diagnosing alpha-gal syndrome.

Methods And Results: Twelve patients with alpha-gal syndrome, 11 patients with immediate beef or pork allergy, 18 asymptomatic individuals with meat sensitization, and 10 non-atopic subjects were enrolled. We checked the levels of sIgE against BTG and cetuximab using the streptavidin CAP assay. Additionally, IgE reactivity to BTG and cetuximab was assessed by immunoblotting. All alpha-gal syndrome patients had a high concentration of sIgE against BTG, and cetuximab. In contrast to alpha-gal syndrome, patients with immediate allergic reactions to meat consumption and those with asymptomatic sensitization had significantly lower concentration of BTG and cetuximab sIgE, and a high prevalence of sIgE against bovine or porcine serum albumin. Although the concentration of sIgE against alpha-gal was lower in individuals with asymptomatic sensitization, IgE immunoblotting showed the presence of sIgE against α-Gal in this group.

Conclusion: Differentiation of alpha-gal syndrome from patients with immediate allergy to meat consumption or asymptomatic sensitization requires quantification of cetuximab- or BTG-induced sIgE via detection of IgE for α-gal.
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http://dx.doi.org/10.1002/mnfr.201601046DOI Listing
October 2017

Soluble CD93 in Serum as a Marker of Allergic Inflammation.

Yonsei Med J 2017 May;58(3):598-603

Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.

Purpose: CD93 is receiving renewed attention as a biomarker of inflammation. We aimed to evaluate the potential for serum sCD93 to serve as a novel biomarker for allergic inflammation.

Materials And Methods: We enrolled 348 subjects with an allergic disease [allergic rhinitis (AR), chronic spontaneous urticaria (CSU), or bronchial asthma (BA)], including 14 steroid-naïve BA patients who were serially followed-up.

Results: The serum sCD93 levels (ng/mL) in patients with exacerbated AR (mean±standard deviation, 153.1±58.4) were significantly higher than in patients without AR (132.2±49.0) or with stable AR (122.3±42.1). Serum sCD93 levels in exacerbated CSU (169.5±42.8) were also significantly higher than those in non-CSU (132.4±51.6) and stable CSU (122.8±36.2). This trend was also seen in BA. Serum levels in patients with ICS-naïve BA (161.4±53.1) were significantly higher than those in healthy controls without BA (112.2±30.8), low- and medium-dose ICS users. Serum sCD93 levels in high-dose ICS users (72.2±20.6) were significantly lower than those in low- and medium-dose users. The serum sCD93 levels in steroid-naïve patients with BA (195.1±72.7) decreased after ICS use for 4 weeks (134.4±42.8) and 8 weeks (100.7±13.4), serially.

Conclusion: Elevated serum sCD93 levels reflected exacerbated status of allergic diseases, including CSU, AR, and asthma. ICS use significantly diminished serum sCD93 levels in steroid-naïve patients with BA. This result may suggest sCD93 in serum as a therapeutic marker for allergic inflammation.
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http://dx.doi.org/10.3349/ymj.2017.58.3.598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368146PMC
May 2017

Adrenal insufficiency associated with long-term use of inhaled steroid in asthma.

Ann Allergy Asthma Immunol 2017 01 7;118(1):66-72.e1. Epub 2016 Nov 7.

Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea.

Background: We previously reported that as many as one third of hospitalized patients with asthma treated with a low to medium daily dose of inhaled steroids (ICSs) for an average of 4.5 years showed adrenal insufficiency (AI).

Objective: To re-examine this issue in consecutive outpatients with asthma because of possible subject selection bias.

Methods: One hundred twenty-one consecutive adult patients with asthma under ICS treatment for at least 6 months underwent a rapid adrenocorticotrophic hormone stimulation test. AI was defined as a morning serum cortisol level no higher than 3 μg/dL or lower than 18 μg/dL before and after administration of 250 μg of adrenocorticotrophic hormone.

Results: The mean durations of ICS use in the short-term (less than the median) and long-term (at least the median) users were 3.8 and 11.5 years, respectively. The proportion of subjects affected by AI tended to increase with the increasing cumulative dose of ICS (short-term users at a low to medium daily dose: mean cumulative dose 502 mg [15 of 34, 44.1%]; short-term users at a high dose of 941 mg [16 of 26, 61.5%]; long-term users at a low to medium dose of 1,077 mg [25 of 41, 61.0%]; long-term users at a high dose of 2,805 mg [13 of 20, 65.0%]), although not significantly. In short-term users, daily and cumulative ICS doses were significantly related to serum cortisol levels 60 minutes after taking adrenocorticotrophic hormone (r = -0.300 and -0.287, respectively; P < .05).

Conclusion: A large number of patients with asthma might have AI even with low- to medium-dose ICS treatment when ICSs are administered over a long period. Thus, it is essential that patients with asthma under ICS treatment be checked for AI much more frequently.
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http://dx.doi.org/10.1016/j.anai.2016.10.002DOI Listing
January 2017

A Case of Type 2 Hereditary Angioedema With SERPING1 Mutation.

Allergy Asthma Immunol Res 2017 Jan;9(1):96-98

Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Hereditary angioedema is a disease of congenital deficiency or functional defect in the C1 esterase inhibitor (C1-INH) consequent to mutation in the SERPING1 gene, which encodes C1-INH. This disease manifests as recurrent, non-pitting, non-pruritic subcutaneous, or submucosal edema as well as an erythematous rash in some cases. These symptoms result from the uncontrolled localized production of bradykinin. The most commonly affected sites are the extremities, face, gastrointestinal tract, and respiratory system. When the respiratory system is affected by hereditary angioedema, swelling of the airway can restrict breathing and lead to life-threatening obstruction. Herein, we report a case of a 24-year-old woman with type 2 hereditary angioedema who presented with recurrent episodic abdominal pain and swelling of the extremities. She had no family history of angioedema. Although her C4 level was markedly decreased (3.40 mg/dL; normal range: 10-40 mg/dL), she presented with a very high C1-INH level (81.0 mg/dL; normal range: 21.0-39.0 mg/dL) and abnormally low C1-INH activity (less than 25%; normal range: 70%-130%). The SERPING1 gene mutation was confirmed in this patient. She was treated with prophylactic tranexamic acid, as needed, and subsequently reported fewer and less severe episodes. To our knowledge, this is the first reported case of type 2 hereditary angioedema in Korea that was consequent to SERPING1 mutation and involved a significantly elevated level of C1-INH as well as a low level of C1-INH activity.
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http://dx.doi.org/10.4168/aair.2017.9.1.96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102842PMC
January 2017

Clinical characteristics of adverse events associated with therapeutic monoclonal antibodies in Korea.

Pharmacoepidemiol Drug Saf 2016 11 30;25(11):1279-1286. Epub 2016 Jun 30.

Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Severance Hospital Regional Pharmacovigilance Center, Yonsei University College of Medicine, Seoul, Korea.

Purpose: The use of monoclonal antibodies (mAbs) is increasing in various clinical fields. Although mAb safety must be demonstrated prior to approval, targeted pharmacovigilance is essential for the recognition and assessment of adverse reactions. The purpose of this study was to identify the major clinical features of adverse reactions to mAbs in Korea.

Methods: Spontaneous reports of adverse reactions attributed to 18 mAbs from January 2005 to December 2014 were extracted from the Korea Adverse Event Reporting System. We analyzed these reports for information relating to patient characteristics and the types of adverse reactions.

Results: In total, 11 492 adverse reactions were reported in 7569 patients. Almost 19% of total study population showed suspected hypersensitivity reactions. Leukocyte abnormalities were reported frequently (10.0%), as well as infections (9.5%), drug eruptions (7.5%), and pruritus (5.0%). Furthermore, 3716 of the adverse reactions in 2538 patients were classified as serious; these included severe infections (18.2%), neutropenia (12.1%), visual dysfunctions (6.6%), and anaphylaxis (4.8%). The mAbs with the highest number of adverse reaction reports were rituximab (27.6%), adalimumab (17.5%), cetuximab (11.9%), and infliximab (10.7%).

Conclusions: Hypersensitivity reactions were observed more frequently than expected, although no previously unrecognized reactions were observed. Adverse reactions occurred more frequently in children and in elderly patients. Close monitoring of adverse reactions to therapeutic mAbs is therefore warranted because these can potentially cause serious medical conditions or death. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pds.4049DOI Listing
November 2016

Different Responses in Induction of Allergen Specific Immunoglobulin G4 and IgE-Blocking Factors for Three Mite Subcutaneous Immunotherapy Products.

Yonsei Med J 2016 Nov;57(6):1427-34

Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Specific immunoglobulin G4 (sIgG4) and immunoglobulin E (IgE)-blocking factors produced by subcutaneous immunotherapy (SCIT) play a critical role in the induction of allergen tolerance. However, comparative studies of available SCIT reagents on the induction of sIgG4 are limited. We compared increases in sIgG4 for three different house dust mite (HDM) SCIT reagents.

Materials And Methods: Seventy-two HDM sensitized allergic patients were enrolled and classified into four groups: 1) control (n=27), 2) SCIT with Hollister-Stier® (n=19), 3) Tyrosine S® (n=16), and 4) Novo-Helisen® (n=10). Levels of specific IgE (sIgE), sIgG4, and IgE blocking factor to Dermatophagoides farinae (D. farinae) were measured using ImmunoCAP (sIgE, sIgG4) and enzyme-linked immunosorbent assay (ELISA) (IgE-blocking factors). Levels were measured before and 13.9±6.6 months after the SCIT. The allergen specificity and the induction levels of sIgE and sIgG4 were confirmed by immunoblot analysis.

Results: After SCIT, sIgG4 levels to D. farinae increased significantly; however, the increases differed significantly among the SCIT groups (p<0.001). Specific IgG4 levels to D. farinae were highest in Hollister-Stier® (3.7±4.1 mg/L), followed by Novo-Helisen® (2.2±2.3 mg/L) and Tyrosine S® (0.7±0.5 mg/L). In addition, patients who were administered using Hollister-Stier® showed the most significant decrease in IgE/IgG4 ratio (p<0.001) and increase in blocking factor (p=0.009). Finally, according to IgE immunoblot results, the Hollister-Stier® group showed the most significant attenuation of IgE binding patterns among others.

Conclusion: Currently available SCIT reagents induce different levels of specific IgG4, IgE/IgG4 ratio, and IgE-blocking factor.
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http://dx.doi.org/10.3349/ymj.2016.57.6.1427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011275PMC
November 2016

Clinical Significance of Component Allergens in Fagales Pollen-Sensitized Peanut Allergy in Korea.

Allergy Asthma Immunol Res 2016 Nov;8(6):505-11

Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Clinical features of peanut allergy can range from localized to systemic reactions. Because peanut and birch pollen have cross-reactivity, peanut can lead to localized allergic reaction in Fagales pollen-sensitized oral allergy syndrome (OAS) patients without peanut sensitization per se. The purpose of this study was to discriminate true peanut food allergy from cross-reactive hypersensitivity in birch-sensitized peanut allergy.

Methods: Birch-sensitized (n=81) and peanut anaphylaxis patients (n=12) were enrolled. Peanut-related allergic reactions and sensitization profiles were examined. Specific IgE to Fagales tree pollens (birch, oak), peanut, and their component allergens (Bet v 1, Bet v 2, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9) were evaluated. Based on these specific IgEs and clinical features, the patients were classified into 4 groups: group 1 (Fagales pollen allergy without OAS), group 2 (Fagales pollen allergy with OAS), group 3 (OAS with peanut anaphylaxis), and group 4 (peanut anaphylaxis).

Results: After peanut consumption, one-third of OAS patients experienced oral symptoms not associated with peanut sensitization. Ara h 1 or Ara h 2 was positive in peanut anaphylaxis patients, whereas Ara h 8 was positive in OAS patients. There were 4 patients with both peanut anaphylaxis and OAS (group 3). Both Ara h 2 and Ara h 8 were positive in these patients. Foods associated with OAS in Korea showed unique patterns compared to Westernized countries.

Conclusions: Ara h 2 and Ara h 8 may be important component allergens for discriminating peanut allergy.
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http://dx.doi.org/10.4168/aair.2016.8.6.505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011050PMC
November 2016

Roflumilast Ameliorates Airway Hyperresponsiveness Caused by Diet-Induced Obesity in a Murine Model.

Am J Respir Cell Mol Biol 2016 07;55(1):82-91

1 Department of Internal Medicine, Division of Allergy and Immunology, and.

Obese patients with asthma respond poorly to conventional asthma medications, resulting in severe symptoms and poor prognosis. Roflumilast, a phosphodiesterase-4 inhibitor that lowers the levels of various substances that are implicated in obese subjects with asthma, may be effective in the treatment of those subjects. We evaluated the potential of roflumilast as a novel therapeutic agent for obese subjects with asthma. We designed three models: diet-induced obesity (DIO); DIO with ovalbumin (OVA); and OVA. We fed C57BL/6J mice a high-fat diet for 3 months with or without OVA sensitization and challenge. Roflumilast or dexamethasone was administered orally three times at 2-day intervals in the last experimental week. Airway hyperresponsiveness resulting from DIO significantly improved in the roflumilast-treated group compared with the dexamethasone-treated groups. Although DIO did not affect the cell proliferation in bronchoalveolar lavage fluid, increased fibrosis was seen in the DIO group, which significantly improved from treatment with roflumilast. DIO-induced changes in adiponectin and leptin levels were improved by roflumilast, whereas dexamethasone aggravated them. mRNA levels and proteins of TNF-α, transforming growth factor-β, IL-1β, and IFN-γ increased in the DIO group and decreased with roflumilast. The reactive oxygen species levels were also increased in the DIO group and decreased by roflumilast. In the DIO plus OVA and OVA models, roflumilast improved Th1 and Th2 cell activation to a greater extent than dexamethasone. Roflumilast is significantly more effective than dexamethasone against airway hyperresponsiveness caused by DIO in the murine model. Roflumilast may represent a promising therapeutic agent for the treatment of obese patients with asthma.
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http://dx.doi.org/10.1165/rcmb.2015-0345OCDOI Listing
July 2016

Pleomorphic adenoma of the trachea.

J Bronchology Interv Pulmonol 2014 Jul;21(3):230-3

Departments of *Internal Medicine †Pathology, Chonnam National University Hospital, Gwangju, Republic of Korea.

Endobronchial pleomorphic adenoma is an extremely rare condition. A 32-year-old woman with exertional dyspnea and cough presented with a carinal mass on chest CT scan. The tumor was successfully removed by rigid bronchoscopy using argon plasma coagulation. Biopsy confirmed the diagnosis of pleomorphic adenoma.
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http://dx.doi.org/10.1097/LBR.0000000000000076DOI Listing
July 2014

Risk factors for patients with stage IVB hepatocellular carcinoma and extension into the heart: prognostic and therapeutic implications.

Yonsei Med J 2014 Mar;55(2):379-86

Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Korea.

Purpose: To evaluate the risk factors of hepatocellular carcinoma (HCC) extension into the right atrium (RA) and determine poor prognostic factors for HCC extension to the heart.

Materials And Methods: A total of 665 patients who were newly diagnosed with HCC were analyzed retrospectively from January 2004 to July 2012. The patients were divided into two groups: 33 patients with HCC extending into the RA and 632 HCC patients during the same period. The patients with HCC extending into the RA were subdivided into shorter survival group (<2 months) and longer survival group (≥2 months).

Results: The prevalence of HCC extending to the RA was 4.96%. In multivariate analysis, a modified Union Internationale Contre le Cancer (UICC) stage higher than IVA, hepatic vein invasion, concomitant inferior vena cava and portal vein invasion, and multinodular tumor type were risk factors for HCC extending to the RA. In multivariate analysis, Cancer of the Liver Italian Program (CLIP) score>3 (p=0.016, OR: 13.89) and active treatment (p=0.024, OR: 0.054) were associated with prognostic factors in patients HCC extending into the RA. Active treatment such as radiation (n=1), transcatheter arterial chemoembolization (TACE) (n=11), Sorafenib (n=1), and combined modalities (n=2) were performed.

Conclusion: Modified UICC stage higher than IVA, vascular invasion and multinodular tumor type are independent risk factors for HCC extending to the RA. Active treatment may prolong survival in patients HCC extending into the RA.
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http://dx.doi.org/10.3349/ymj.2014.55.2.379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936619PMC
March 2014

Predictive factors for recurrence and survival in hepatocellular carcinoma in South Korea.

Anticancer Res 2013 Sep;33(9):4129-34

Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, Dong-Ku, Gwangju, Korea.

Aim: To evaluate the factors predicting for recurrence and to analyze survival of patients with hepatocellular carcinoma (HCC).

Patients And Methods: A total of 743 patients who were consecutively diagnosed and treated with HCC were retrospectively analyzed from January 2004 to December 2012 at our institution. We analyzed their survival and tumor recurrence.

Results: On multivariate analysis, age >50 years, CLIP score <3, ALP <120 U/l, LDH <450 IU/l, CRP <0.8 mg/dl, tumor size <6 cm, no distant metastasis, and curative treatment modality were predictors for 1-year survival. CRP <0.8 mg/dl, Child-Pugh score <7, curative treatment modality and tumor size <6 cm were predictors for 3-year survival. Absence of vascular invasion and uninodular tumor type were predictors for 5-year survival. Multinodular tumor, tumor size >4 cm, and palliative treatment were independent risk factors for 1-year recurrence after initial treatment.

Conclusion: This large study provides a comprehensive overview of the survival outcomes and prognostic factors regarding HCC, according to clinical characteristics, various treatment modalities, and the results will help in the selection of effective treatment strategies future.
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September 2013
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