비알코올성 지방간의 새로운 치료 표적: 염증성 대식세포의 Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2와 Reactive Oxygen Species

은혁수 ( Hyuk Soo Eun ) 대한소화기학회 2018 대한소화기학회지 Vol.72 No.4

비알코올성 지방간 발생의 여러 원인들 중에서 염증세포들에서의 활성산소종(reactive oxygen species)의 발생은 지방간 질환과 인슐린 저항성의 주요 원인들 중 하나이다. 이들 활성산소는 대부분이 간으로 침윤된 대식세포로부터 유래되는데 특히 니코틴아미드 아데닌 디뉴클레오티드인산염 산화효소(nicotinamide adenine dinucleotide phosphate oxidase, NOX)에 의하여 주로 발현된다. 그중에서도 간내 염증세포 내에서 NOX를 매개로 활성산소가 발생할 수 있음은 잘 알려졌으나 어떤 세포에서 주로 활성산소가 발생하는지와 어떠한 기전으로 NOX2가 지방간병증과 인슐린 저항성에 기여하는지에 관한 자세한 내용은 알려지지 않았다. 본 연구에서는 NOX2를 발현하는 대표적인 간내 염증세포들로서 호중구, 간내 거주 쿠퍼세포, 간으로 이행한 대식세포 등 여러 세포 유형들 중에서, 주로 간으로 이행된 대식세포에서 NOX2를 매개로 활성산소를 생산하고 있다는 사실을 밝혀내었다. 이 같은 내용은 사람과 마우스의 간내 면역세포들을 분리하여 활성산소를 측정할 수 있는 방법인 2,7-Dichlorodihydrofluorescein acetate (DCFDA)를 이용하여 사람에서는 CD68^highCD14^low 쿠퍼세포가 아닌 CD68^lowCD14^high 대식세포에서 주로 활성산소를 발현하며, 마우스에서는 CD11b⁺F4/80^high 쿠퍼세포가 아닌 CD11b⁺F4/80^low대식세포에서 대부분의 활성산소를 발생시키고 있음을 증명하였다. 한편, lipopolysaccharide (LPS)-toll-like receptor 4(TLR4) 복합체의 내포 작용(endocytosis) 과정과 유사하게, 마우스 대식세포와 사람 단핵구에서 팔미트산(palmitate)은 다이나민(dynamin)을 매개로 팔미트산염의 내포 작용이 이루어진다. 서로 다른 지질 리간드들과 TLR4-myeloid dif-ferentiation factor 2 (MD2) 복합체와의 상호 작용을 크기 배제 크로마토그래피(size-exclusion chromatography)와 에스디에스 페이지(SDS-PAGE) 방법을 이용하여 분석한 결과, TLR4-MD2와 이합체(dimeric)로 결합하는 LPS와는 다르게 팔미트산은 상기 수용체와 단량체(monomeric) 형태로 나타남을 확인하였다. 또한, 정상 마우스와 비교하였을 때 TLR4 결여 마우스, NOX2 결여 마우스의 대식세포에서는 팔미트산 처리 시에 활성산소의 발생이 현저히 감소하지만, Myd88/Toll/Interleukin-1 receptor-domain-containing adapter-inducing interferon-β (TRIF) 결여 마우스의 대식세포에서는 활성산소의 발생이 전혀 감소하지 않는 결과를 보였다. 종합하면, 대식세포의 주 염증 매개체인 LPS가 TLR4-MD2복합체와 이합체의 형태로 결합되어 Myd88 혹은 TRIF 의존적으로 염증성 신호 전달을 하는 것과 다르게, 장관에서 흡수되거나 지방조직으로부터 용해된 혈중 유리지방산(free fatty acid)의 일종인 팔미트산의 경우 TLR4-MD2 복합체와 결합 후 단량체의 형태로 내포 작용이 이루어지며, Myd88과 TRIF 비의존적으로 특이적 활성산소가 발생함을 본 연구에서 보여주었다. 결론적으로 본 연구는 비알코올성 지방간 질환 발생시 이행성 대식세포들에서 팔미트산과 결합하는 TLR4의 내포 작용을 억제할 경우 활성산소의 발생을 감소시킬 수 있음을 증명한 첫 연구이다.

Cons: Statin (HMG-CoA reductase inhibitors) for portal hypertension

은혁수 ( Hyuk Soo Eun ) 대한간학회 2017 간학회 싱글토픽 심포지움 Vol.2017 No.2

Over the past 30 years, statins have been widely used for dyslipidemia. In addition to lipid-lowering roles, statins have pleiotropic effects on various diseases. Recently, the use of statins in patients with portal hypertension have been actively investigated, and situation in which statins may aggravate the disease will be discussed. In addition, we will discuss the possible side effects of statins in patients with underlying chronic liver disease or liver cirrhosis. In case of chronic liver injury, hedgehog signaling pathway is activated by various hedgehog ligands secreted by injured cells and the portal hypertension is exacerbated. Here, when portal hypertension is accompanied by liver cirrhosis, statin effectively reduces portal hypertension by inhibiting its molecular target. However, if there was no cirrhosis, but only portal hypertension is existed, it is reported that portal hypertension is aggravated when statin used. Therefore, statin use should be done selectively through sufficient consideration of the underlying disease of the patients. Moreover, the use of statins may lead to hepatotoxicity, drug-induced liver injury, and myopathies, especially in patients with chronic liver disease or cirrhosis in base.

중증 또는 비전형적 지역사회획득 폐렴으로 입원한 환자에서 호흡기 바이러스 의 검출 빈도

박지원 ( Ji Won Park ),정선영 ( Sun Young Jung ),은혁수 ( Hyuk Soo Eun ),천신혜 ( Shin Hye Cheon ),성석우 ( Seok Woo Seong ),박동일 ( Dong Il Park ),박명린 ( Myung Rin Park ),박희선 ( Hee Sun Park ),정성수 ( Sung Soo Jung ),김주옥 대한결핵 및 호흡기학회 2011 Tuberculosis and Respiratory Diseases Vol.71 No.5

Background: Community-acquired pneumonia (CAP) is an important cause of morbidity and mortality throughout the world in all age groups. Viral causes of CAP are less well characterized than bacterial causes. We analyzed the characteristics of hospitalized patients with CAP who had a viral pathogen detected by multiplex polymerase chain reaction (PCR). Methods: Multiplex real-time PCR was performed for respiratory viruses in samples collected from 520 adults who developed CAP at Chungnam National University Hospital. Clinical, laboratory, and radiological features at presentation as well as other epidemiological data were analyzed. Results: Of 520 patients with CAP, a viral pathogen was detected in 60 (11.5%), and influenza A was the most common. The virus detection rate in patients with CAP was highest in November. Two or more pathogens were detected in 13 (21.7%) patients. Seven patients had severe disease and were administered in the intensive care unit. Most patients (49/60, 81.7%) had comorbidities. However, nine (15%) patients had no comorbidities, and their age was <60 years. The ground glass opacity pattern was the most common radiological feature. Seven (11.7%) patients died from CAP. Conclusion: Viral pathogens are commonly detected in patients with CAP, and a respiratory virus may be associated with the severity and outcome of pneumonia. Careful attention should be paid to the viral etiology in adult patients with CAP.

Streptococcus parasanguinis에 의한 폐렴과 부폐렴성 흉수

박명린 ( Myoung Rin Park ),박동일 ( Dong Il Park ),유수진 ( Su Jin Yoo ),정선영 ( Sun Young Jung ),은혁수 ( Hyuk Soo Eun ),김민정 ( Min Jung Kim ),박지원 ( Ji Won Park ),박희선 ( Hee Sun Park ),정성수 ( Sung Soo Jung ),김주옥 ( Ju 대한결핵 및 호흡기학회 2011 Tuberculosis and Respiratory Diseases Vol.71 No.5

Streptococcus parasanguinis is a Viridans group bacteria that is most often discovered in the oral cavity and causes dental plaque and endocarditis in a rat model. It has low virulence but an unknown relationship to human respiratory infections. We report on a 61-year-old woman who developed hemoptysis followed by pleuritic chest pain after conscious sedation during a gastroscopic polypectomy and was diagnosed with pneumonia and parapneumonic effusion from Streptococcus parasanguinis isolated in pleural fluid. Microaspiration during the procedure was presumed to play a role in the pathogenesis.

증례 : 위험인자가 없는 환자에서 발생한 Serratia grimesii에 의한 감염성 척추염 1예

천신혜 ( Shin Hye Cheon ),손경목 ( Kyung Mok Sohn ),김연숙 ( Yeon Sook Kim ),정현 ( Hyeon Jung ),은혁수 ( Hyuk Soo Eun ),최승원 ( Seung Won Choi ),구선회 ( Sun Hoe Koo ) 대한내과학회 2012 대한내과학회지 Vol.83 No.1

Serratia에 의한 감염은 대부분 병원 시술이나 수술 혹은 면역 저하와 관련되어 있다. 인간 감염을 일으키는 것으로 S. marcescens가 가장 흔하고 S. liquefaciens도 종종 문제가 된다. 그러나 S. gimesii에 의한 감염 혹은 지역사회 획득 Serratia 척추염은 보고된 적이 없다. 저자들은 고혈압 외에는 건강하게 지내던 환자에서 발생한 경막외 고름을 동반한 S. grimesii에 의한 척추 골수염을 경험하였다. 고름 제거 후 항생제 치료로 호전되어 문헌고찰과 함께 보고하는 바이다. Vertebral osteomyelitis or paraspinal abscess caused by Serratia species is rare and has been reported only in certain groups of people, such as intravenous drug users, immunocompromised hosts, and patients who have undergone invasive procedures. However, we report here that Serratia was recovered from a patient with vertebral osteomyelitis and epidural abscess without predisposing factors. The organism was initially identified as Serratia liquefaciens by a Vitek II-based assessment. It was finally identified as Serratia grimesii by 16S rRNA gene sequence analysis. We present the first case of vertebral osteomyelitis caused by S. grimesii in a patient without risk factors and who was managed successfully.

만성 C형 간염에서 페그인터페론과 리바비린의 병합치료시 치료 순응도의 중요성

이헌영 ( Heon Young Lee ),고평곤 ( Pyung Gohn Goh ),김민정 ( Min Jung Kim ),김혜진 ( Hye Jin Kim ),은혁수 ( Hyuk Soo Eun ),김의식 ( Eui Sik Kim ),김윤정 ( Yun Jeung Kim ),이수윤 ( Soo Youn Lee ),문희석 ( Hee Seok Moon ),이엄석 ( E 대한소화기학회 2011 대한소화기학회지 Vol.57 No.5

Background/Aims: The combination therapy with peginterferon and ribavirin is a standard treatment for patients with chronic hepatitis C. However, because of the long duration of the treatment and many complications, the reduction of adherence frequently occur. This study aimed to assess influences of reduced medication adherence in the combination therapy of chronic hepatitis C patients. Methods: We retrospectively reviewed the medical records of 82 patients with chronic hepatitis C who received a combination therapy with peginterferon and ribavirin. The patients were categorized into 3 subgroups on the basis of medication adherence. Group 1 comprised patients who received ≥80% of the recommended dosage of both peginterferon and ribavirin. Group 2 comprised those patients who received ≥80% of the recommended dosage of only 1 drug. The patients of Group 3 received <80% of the recommended dosage of both the drugs. Results: Sustained virologic response (SVR)s of patients in Group 1, 2 and 3 were 85.4% (41/48), 85.7% (18/21), and 38.5% (5/13), respectively (p=0.002). SVRs of genotype 1 patients in Group 1, 2 and 3 were 84.2% (16/19), 75% (9/12), and 14.3% (1/7), respectively (p=0.003). SVRs of genotype non-1 patients in Group 1, 2 and 3 were 86.2% (25/29), 100% (9/9), and 66.7% (4/6), respectively (p=0.196). Furthermore are SVRs significantly differed with the degree of medication adherence to either peginterferon or ribavirin (p=0.003 and 0.021, respectively). In multivariate analysis, the peginterferon dose was a significant independent factor associated with SVR. Conclusions: Medication adherence of chronic hepatitis C patients to the combination therapy with peginterferon and ribavirin is very important for achieving SVR. In particular, we think that genotype 1 patients should maintain higher adherence than genotype non-1 patients. (Korean J Gastroenterol 2011;57:294-301)

유전자형 1형과 2형의 한국인 만성 C형간염 환자에서 Glecaprevir/Pibrentasvir와 Sofosbuvir/Ledipasvir의 비교

신현덕 ( Hyun Deok Shin ),송일한 ( Il Han Song ),이세환 ( Sae Hwan Lee ),김홍수 ( Hong Soo Kim ),이태희 ( Tae Hee Lee ),은혁수 ( Hyuk Soo Eun ),김석현 ( Seok Hyun Kim ),이병석 ( Byung Seok Lee ),채희복 ( Hee Bok Chae ),김석환 ( Se 대한소화기학회 2024 대한소화기학회지 Vol.83 No.3

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C. (Korean J Gastroenterol 2024;83:111-118)