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최신 연구 소개 : 비알코올 지방간염의 조직학적 호전이 약물 치료로 가능한가?
허내윤 ( Nae Yun Heo ) 대한소화기학회 2016 대한소화기학회지 Vol.67 No.5
Farnesoid X Nuclear Receptor Ligand Obeticholic Acid for Non-cirrhotic, Non-alcoholic Steatohepatitis (FLINT): a Multicentre, Randomised, Placebo-controlled Trial (Lancet 2015;385:956-965) Liraglutide Safety and Efficacy in Patients with Non-alcoholic Steatohepatitis (LEAN): a Multicentre, Double-blind, Randomised, Placebo-controlled Phase 2 Study (Lancet 2016;387:679-690)
허내윤 ( Nae-yun Heo ) 대한내과학회 2023 대한내과학회지 Vol.98 No.2
An evaluation of liver fibrosis severity during the initial examination is essential for the determination of chronic liver disease prognosis. Although liver biopsy is the gold standard for evaluation of liver fibrosis, bleeding can occur. Therefore, several non-invasive approaches have been introduced, including an equation with clinical variables and assessments of liver stiffness (e.g., elastography). Most patients with chronic liver disease can undergo evaluation of liver fibrosis severity without a liver biopsy using these alternative methods. (Korean J Med 2023;98:84-87)
Prevention of vertical transmission with NUC: Indication and clinical practice
허내윤 ( Nae-yun Heo ) 대한간학회 2017 간학회 싱글토픽 심포지움 Vol.2017 No.1
Although the immunoprophylaxis with vaccination and immunoglobulin has been introduced to reduce the risk of vertical transmission of hepatitis B virus (HBV) from mother to child during perinatal period, 1-14% of the neonate experience the failure of prevention. Maternal HBeAg positivity and high viral load (HBV DNA >200,000 IU/mL) were known as the major risk factors of vertical transmission. Several studies showed that when antiviral nucleos(t)ide analogues (NUCs) started during second or third trimester in the pregnant women who had a high viral load, almost all neonate can escape the vertical transmission without significant birth defect. However, the sophisticated studies are required to determine the long-term effect on the child who expose to NUC during pregnancy.
C형간염 관련 간세포암종 환자에게서 경구 직접작용 항바이러스제 치료의 위험과 이득
허내윤 ( Nae-yun Heo ) 대한간학회 2020 Postgraduate Courses (PG) Vol.2020 No.1
Since the introduction of direct-acting antiviral agents (DAA) for chronic hepatitis C, sustained virologic response rate has steeply elevated. Theoretically, effective antiviral treatment may pose a positive impact in the patients with hepatocellular carcinoma who had a curative treatment because virologic cure can result in the regression of fibrosis and improvement of portal hypertension. However, a few recent studies suggested the unexpected high HCC recurrence after DAA treatment, which induced a hot issue, and subsequent studies showed inconsistent results. Although considering the many limitations of available studies, there is no strong evidence of increased risk of HCC recurrence after DAA treatment right now. Therefore, at present, it is prudent to perform DAA treatment in the patients with curative treatment for HCC at the point that their complete response becomes more certain.
허내윤 ( Nae-yun Heo ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
The occurrence of ascites is one of major signals which indicate that the patients with liver cirrhosis arrive at the stage of decompensation. Although portal hypertension is the most frequent cause of ascites in case of cirrhosis, other causes should be evaluated meticulously such as malignancy, tuberculosis, and congestive heart failure through the ascetic fluid analysis. If the cirrhotic patient presents abdominal distention and complaint of abdominal pain or fever, diagnostic paracentesis is urgent to find out the spontaneous bacterial peritonitis. The general measures to control the large volume of ascites include the low salt diet, diuretics, and therapeutic paracentesis in addition of treatment of underlying liver disease. Refractory ascites is difficult to control by diuretics, and liver transplantation should be considered. In this case, transjugular intrahepatic portosystemic shunt may be a helpful bridge therapy. Clinicians are required to know that the control of ascites is one of most valuable treatments to improve the quality of life in cirrhotic patient, and apply the adequate method effectively.
진행성 간세포암종에서 면역관문억제제와 표적항암제 병합요법의 임상 성적: 소라페닙 시대가 저물다
허내윤 ( Nae-yun Heo ) 대한소화기학회 2021 대한소화기학회지 Vol.77 No.3
최근 진행성 간세포암종에 관하여 표적항암치료제와 면역관문억제제 병합요법이 환자 생존을 향상시킬 수 있을 것이라는 기대가 있었고, programmed death-ligand 1 (PD-L1) 억제제인 atezolizumab과 vascular endothelial growth factor (VEGF) 수용체에 관한 단일클론 항체인 bevacizumab 병합이 1b상 연구에서 효과와 안전성이 입증되어 이들 병합요법을 기존 표준 요법인 sorafenib과 비교하는 다기관 무작위 3상연구가 진행되었다.1 본 연구는 18세 이상 국소적으로 진행한전이성 혹은 절제 불가능한 간세포암종 환자를 대상으로 하여, 치료군은 atezolizumab 1,200 mg, bevacizumab 15 mg/kg을 매 3주마다 정맥 주사하였고, 대조군은 sorafenib 400 mg을 하루 2회 경구 투여하였다. 투약 기간은 부작용을 감당하기 어렵거나, 임상적 이득이 없다고 판단될 때까지로 설정하였다. 공통 일차평가지표는 전체 생존(overall survival)과 RECIST 1.1 기준에 따른 무진행 생존(progression-free survival)이었다. 2019년 8월 말까지 데이터로 1차 중간 분석을 한 결과 중앙값 8.6개월 추적 후 치료군 336명 중 96명(29%), 대조군 165명 중 65명(39%)이 사망하였고(사망에 관한 위험비 0.58; 95% 신뢰구간 0.42-0.79; p<0.001), 같은 기간 동안 종양이 진행하였거나 사망한 경우는 치료군 중 197명(59%), 대조군중 109명(66%) (종양 진행 및 사망 위험비 0.59; 95% 신뢰구간 0.47-0.76; p<0.001)으로 전체 및 무진행 생존 모두 치료군이 대조군에 비해 유의하게 높았다. 객관적 반응률은 RECIST 1.1기준으로 평가할 때 치료군에서 27%, 대조군에서 12%, 변형 RECIST 기준으로 평가할 때 치료군에서 33%, 대조군에서 13% 였고, 두 군 간 통계적으로 유의한 차이가 있었다. 질병통제율(객관적 반응 및 안정 병변)은 치료군에서 74%, 대조군에서 55%였다. 삶의 질 평가 지표(EORTC QLQ-C30) 악화까지 걸린 기간은 치료군에서 11.2개월, 대조군에서 3.6개월(위험비 0.63; 95% 신뢰구간 0.46-0.85)로 차이가 있었다. 투약기간의 중앙값은 atezolizumab은 7.4개월, bevacizumab은 6.9개월, sorafenib은 2.8개월이었다. 치료군에서 가장 흔하게 발생한 3등급 혹은 4등급 이상반응은 고혈압으로 15%에서 발생하였다. 이상반응으로 인해 한 가지 이상 약제 투약이 중단된 경우는 치료군에서 15.5%, 대조군에서 10.3%였다.
대사증후군 요소와 관련된 만성 간질환에서 Biphenyl Dimethyl Dicarboxylate와 Ursodeoxycholic Acid 병합요법의 효과 및 안전성
허내윤 ( Nae-yun Heo ),박승하 ( Seung Ha Park ),최준혁 ( Joon Hyuk Choi ),김은주 ( Eunju Kim ),김태오 ( Tae Oh Kim ),박종하 ( Jongha Park ),이진 ( Jin Lee ),박용은 ( Yong Eun Park ),오은혜 ( Eun Hye Oh ),황준성 ( Jun Seong Hwang 대한소화기학회 2021 대한소화기학회지 Vol.77 No.4
Background/Aims: Steatohepatitis related to metabolic syndrome is a chronic liver disease prevalent in patients not only with non-alcoholic steatohepatitis but also with alcoholic liver disease and chronic viral hepatitis. On the other hand, there is limited data on the effects of hepatotonic agents in these patients. Therefore, this study evaluated the efficacy of a combined hepatotonic agent in this population. Methods: Thirty-three adults with chronic hepatitis and one or more components of metabolic syndrome were assigned randomly to receive biphenyl dimethyl dicarboxylate/ursodeoxycholic acid or a placebo for 24 weeks. The primary outcome was the normalization of ALT (≤40 U/L). The secondary outcomes were the change in controlled attenuation parameter, transient elastography, and Chronic Liver Disease Questionnaire score. Results: The 33 patients were assigned randomly to two groups. Eight (50%) of 16 patients who received the intervention drug showed the normalization of ALT, whereas only one (6%) of 17 patients in the placebo group did so. In contrast, the change in controlled attenuation, transient elastography, and Chronic Liver Disease Questionnaire were similar in the two groups. ALT was changed significantly during the four assessment periods, and this change was affected by the group. The interaction between the group and time was also significant. AST was changed significantly during the same period. This change was not affected by the group. Conclusions: Biphenyl dimethyl dicarboxylate/ursodeoxycholic acid combination reduced ALT in chronic liver disease related to metabolic syndrome. On the other hand, there is no evidence that this leads to improved hepatic steatosis and fibrosis within 6 months. (Korean J Gastroenterol 2021;77:179-189)