만성 B형 간염환자의 간조직에서의 Fas 항원의 발현

홍성표(Sung Pyo Hong),김경철(Kyung Chul Kim),차영수(Young Soo Cha),최윤정(Yoon Jung Choi),국진환(Jin Whan Guk),최유정(Yu Jung Choi),김배영(Bae Young Kim),박필원(Pil Won Park),임규성(Gyu Sung Im) 대한소화기학회 1998 대한소화기학회지 Vol.31 No.2

Backgroud/Aims: Liver damage in chronic B viral hepatitis depends on host immune response, not direct toxicity. Fas-Fas ligand interaction induced apoptosis plays an important role in liver damage from viral hepatitis. In the present study, we examined the incidence of Fas antigen expression, concordancy between Fas antigen (Ag) and hepatitis B surface antigen (HBsAg) expression, and finally correlation of Fas Ag expression with histological activity index in liver tissue of patients with chronic B viral hepatitis. Methods: We studied liver biopsy samples from 59 patients (chronic active B viral hepatitis 40 cases, chronic persistent R viral hepatitis 10 cases, normal control 9 cases). We evaluated immunohistochemically the expression of Fas Ag and HBsAg with anti-Fas Ag monoclonal IgM antibody and anti-HBsAg polyclonal IgG antibody respectively in liver tissue. Results: Fas Ag was expressed in 9 among 10 cases (90%) of chronic persistent B viral hepatitis and 34 among 40 cases (85%) of chronic active B viral hepatitis, but none in the normal control group. Fas Ag was diffusely expressed in 67.6% of chronic active B viral hepatitis and 33.3% of chronic persistent B viral hepatitis. The cases which showed diffuse expression of Fas Ag tend to have higher transaminase levels, and higher histological activity indexes. The concordancy between Fas Ag and HBsAg expression was 62.8% and it tended to be higher in diffusely or multifocally expressed group of Fas Ag. Conclusions: The Fas Ag expression in hepatocytes may be induced by hepatitis B virus infection and it was correlated with histological activity index. Liver damage in chronic B viral hepatitis may be related to Fas Ag mediated host immune response. (Korean J Gastroenterol 1998;31:204-211)

만성 바이러스성 간염 환자의 간조직에서 Fas 항원의 면역조직화학적 관찰

남순우(Soon Woo Nam),최상욱(Sang Wook Choi),최황(Hwang Choi),김병욱(Byung Wook Kim),김성수(Sung Soo Kim),양진모(Jin Mo Yang),한남익(Nam Ik Han),이창돈(Chang Don Lee),차상복(Sang Bok Cha),정규원(Kyu Won Chung),선희식(Hee Sik Sun) 대한소화기학회 1999 대한소화기학회지 Vol.34 No.5

Background/Aims: Fas was proposed as a protein that triggers or mediates apoptosis combining with Fas ligand on cytotoxic T lymphocytes. The mechanism of hepatic injury in chronic viral hepatitis may also include Fas-mediated apoptosis. We evaluated the expression patterns of Fas in liver tissues of patients with chronic viral hepatitis. Methods: Eighty-six liver biopsy samples from patients with chronic viral hepatitis (64 HBsAg positive, 22 anti-HCV positive) were immunohistochemically stained for Fas. Histological findings were evaluated according to the Knodell's Histologic Activity Index (HAI). Results: Incidence of Fas-positive hepatocytes in chronic viral hepatitis was 75.5% (75% in type B and 77.2% in type C). Hepatocellular localization of Fas expression in hepatitis B was the membrane in 89.5% of the patients and the cytoplasm in 87.5% of them. In hepatitis C, it was the membrane in all cases and the cytoplasm in 76.4%. Fas positive hepatocytes were the most frequently detected in periportal area. The prevalence of Fas expression was 100% in chronic active hepatitis of both type B and type C, while in chronic persistent hapatitis, it was 68.8% in type B and 73.3% in type C. There was a positive relationship between the grade of Fas expression and HAI score. Conclusions: Hepatocytic apoptosis associated with Fas expression may play a role in the pathological mechanism of the hepatic injury in chronic viral hepatitis. (Kor J Gastroenterol 1999;34:644 - 651)

만성 B형 간염환자의 간조직에서의 Fas 항원의 발현

차영수,홍성표,최윤정,국진환,최유정,김경철,김배영,박필원,임규성 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.31 No.2

만성 바이러스 간염 환자에서 간조직의 철과 구리 농도

김형욱(Hyong Wook Kim),김태오(Tae Oh Kim),류수형(Soo Hyoung Ryu),강대환(Dae Hwan Kang),송철수(Chul Soo Song),송근암(Guen Am Song),조몽(Mong Cho),양웅석(Ung Suk Yang) 대한소화기학회 1999 대한소화기학회지 Vol.34 No.4

Background/Aims: In viral hepatitis, it is unclear whether iron and copper play a role in the pathogenesis of hepatic injury. The purpose of this study was to investigate the presence of correlation between the hepatic concentrations of these metals and the grades of inflammation or stages of fibrosis in patients with chronic viral hepatitis. Methods: This study included 53 patients consisting of 44 patients with chronic hepatitis B, 6 patients with chronic hepatitis C, and 3 patients with cirrhosis. Hepatic iron and copper concentrations were determined by Inductively Coupled Plasma- Atomic Emission Spectrometry. Results: Average hepatic iron concentration was 583.2±606.5 μg/g dry weight. In one patient (1.9%), hepatic iron concentration was unusually high (4573.0 μg/g dry weight). Hepatic iron concentrations were not different according to the grade of portal/periportal and lobular inflammation, or the stage of fibrosis. Average hepatic copper concentration was 65.3±35.3 μg/g dry weight and hepatic copper concentrations were increased in 25 patients (47.2%). Hepatic copper concentrations were significantly related with the grade of portal/periportal inflammation (rs=0.475, p<0.001), lobular inflammation (rs=0.362, p=0.008), and the stage of fibrosis (rs=0.410, p=0.002). Conclusions: These results suggest that copper may have an important role as a cofactor in the pathogenesis of hepatic injury in chronic viral hepatitis. (Kor J Gastroenterol 1999;34:489 - 495)

만성 바이러스성 간염의 치료

이민호 한양대학교 의과대학 1998 한양의대 학술지 Vol.18 No.1

Chronic viral hepatitis is the principal cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. In Korea, of the known hepatits viruses, two can chronic hepatitis: the hepatits B virus(HBV) and the hepatits C virus(HCV). In chronic hepatitis B, a 4-6 month course of interferon alfa is effective in inducing clearlance of HBV DNA and HBeAg from serum and an improvement in serum transaminase concentration. New approaches to theraphy for hepatitis B include lamivudine and famiciclovir. In chronic hepatitis C, characterized by an indolent course, but with the potential for development of serious consequences. At present, the only approved agent is interferon alfa, with a sustained biochemical response rate of 10-22%. New approach to therapy for hepatitis C include combination theraphy with interferon alfa and ribavirin. In this article, strategies for treatment development of chronic B hepatitis and chronic C hepatitis are reviewed.

How Many Valid Measurements Are Necessary to Assess Liver Fibrosis Using FibroScan® in Patients with Chronic Viral Hepatitis? An Analysis of Subjects with at Least 10 Valid Measurements

장희원,김도영,김승업,박준용,안상훈,한광협,전재윤,박영년,최은희 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.2

Purpose: Using FibroScan® to obtain a reliable liver stiffness measurement (LSM) may require more than 10 valid measurements (VMs), according to the manufacturer’s recommendations. However, this requirement lacks scientific evidence in support thereof. We investigated the minimal number of VMs required to assess liver fibrosis without significant loss of accuracy in patients with chronic hepatitis B (CHB) and C (CHC) and predictors of discordance between LSM and liver biopsy (LB). Materials and Methods: Between January 2005 and December 2009, we prospectively enrolled 182 patients with CHB and 68 patients with CHC who were to undergo LB and LSM before starting antiviral treatment. Only LSMs with at least 10 VMs were considered reliable. The Batts and Ludwig scoring system was used for histologic assessment. Results: The mean age and body mass index were 46.0 years and 23.4 kg/m2 in patients with CHB and 49.7 years and 23.1 kg/m2 in those with CHC, respectively. The median elasticity scores from the first 3, first 5, and all VMs taken significantly predicted fibrosis stages ≥F2 and F4 (all p<0.05) without significant differences (all p>0.05 by DeLong’s method). Alanine aminotransferase (ALT) was the only predictor of discordance in fibrosis stage as estimated by the median elasticity score from the first 3 VMs and by LB in patients with CHB, whereas no significant predictor was identified in those with CHC. Conclusion: After comparison of patients who had more than 10 valid measurements for LSM, three VMs may be enough to assess liver fibrosis using LSM without significant loss of accuracy in patients with CHC and patients with CHB. However, ALT should be considered when interpreting LSM for patients with CHB.

Interferon과 Ribavirin 병용요법 시행중인 만성 C형간염 환자에서 발생한 부작용에 대한 침구치료 증례

김성환,홍상훈,박동일,Kim, Sung-hwan,Hong, Sang-hoon,Park, Dong-il 대한침구의학회 2003 대한침구의학회지 Vol.20 No.1

Objective : Interferon-alpha and Rivabirin are much used at the same time to treat Chronical C viral hepatitis. But interferon caused lots of unexpected side effects, Acupuncture Treatment for them will be an alternative plan. Methods : We first posed questions to a 4 year-old man who ha skin flare, fatigue, itching, insomnia, pronounced a diagnosis based on overall of symptoms and signs and then treated Acupuncture, Moxibustion and Electroacupuncture. We acupunctured a BL17, BL18, BL20 and removed it at once. We electroacupunctured at GV20, Yin tang(Ex-HN3) form 20 minutes, acupunctured at Bi yi(鼻翼, Extra-point), S36, P6. Pizhengge(脾定格) was acupunctured for 10 minutes. Results : The symptoms of fatigue, insomnia, itching are reduced after acupuncture treatments and they made a person keep interferon treatment on. Conclusions : We confirmed that acupuncture treatments make a patient of chronic C viral hepatitis reduce and improve side effects of interferon treatment. We should keep on studying the various and efficient method of acupuncture treatment to improve living quality and treatment efficiency of patients.

만성(慢性) B형(型) 간염환자(肝炎患者) 삶의 질(質)

김헌수,이민규,Kim, Hun-Soo,Lee, Min-Kyu 한국정신신체의학회 1998 정신신체의학 Vol.6 No.1

Objectives : The purpose of this study was to determine correlation between coping strategies to disease and quality of life in chrome viral B hepatitis patients ; to investigate difference of coping strategies to disease and quality in life between chronic viral B hepatitis patients and normal persons ; and to identify major variables related to quality in life of chronic viral B hepatitis patients. Methods: The authors used Weisman coping strategy scale for measuring coping ability and efficacies, and the questionnaire for measuring quality of life including physical, psychological, social and economical aspects and satisfaction of sexual life was made by authors based on related literatures. Data were collected through questionnaire survey over a period from Sep 15, 1994 to Nov 11, 1994. Subjects served for this study consisted of 94 chronic viral B hepatitis patients visited to department of internal medicine at one general hospital and 100 normal persons visited to one general hospital for routine check up of health. The collected data were analyzed by SAS and the statistical methods for analysis were Chisquare, t-test and multiple regression analysis. Results : 1) It was revealed that coping strategies to disease significantly correlated to individual's quality of life. 2) There was no significant difference in coping strategies to disease between chronic viral B hepatitis patients and normal persons. However, chronic viral B hepatitis patients showed the lower scroes of quality of life in physical, psychological and economical aspects. 3) The most important variables which were influenced upon quality of life were coping strategies to disease and satisfaction of sexual life. That is, the more active coping strategies to diseases and the higher satisfaction of sexual life, consequently the higher quality of life was. Especially male patient group or normal persons showed each other the higher scores of quality of life in physical and psychological area than female group or patient group. 4) No statistically significant difference in coping strategies to disease and quality of life was found between HBeAg positive group and HBeAg negative group. Conclusions : The authors suggest that chronic viral B hepatitis patients may show the lower score of quality of life than normal person. Therefore, quality of life assessment should become an integral part of all clinical area that seek to assess the effectiveness of treatment. Also, through the interdisciplinary approach, a comprehensive paradigm that can better account for the effects of chronic disease on the individual' s quality of life should be developed.

HbeAg 음성인 만성 B형 간염 환자에서 라미부딘 투여중 Viral Breakthrough의 발생 빈도

장윤정,임정윤,조남영,최창원,백수정,안수현,최도원,권용대,김선숙,권오상,김주현,연종은,송진원,변관수,이창홍 대한간학회 2002 Clinical and Molecular Hepatology(대한간학회지) Vol.8 No.4

목적: 라미부딘 치료는 HBeAg 양성 만성 B형 간 염환자에서 효과적인 것으로 알려져 있지만 HBeAg 음성 만성 B형 간염 환자에서 장기간의 치료효과와 BT의 발생률은 아직 확실치 않다. 이에 HBeAg 존재유무에 따른 BT의 발생률을 비교하고 BT의 발생과 YMDD 변이종의 출현과의 관계를 확인하고자 하였다. 대상과 방법: 최소한 9개월이상 라미부딘을 투여받은 만성 B형 간염 환자를 대상으로 하였으며 HBeAg 양성군은 205명, HBeAg 음성군은 49명이었다. 라미부딘 치료기간은 HBeAg 양성군 176개월, HBeAg 음성군은 155개월으로 양군 간에 차이가 없었다. YMDD 변이종은 RFLP 분석과 직접 염기서열 분석으로 확인하였다. 결과: 대상 군의 임상적 특성은 HBeAg 음성군이 양성군에 비해 나이는 더 많았고(43±9세 vs. 39±10세; p<0.05) 치료전 HBV DNA 역가가 낮았다(670±1499 vs. 1877±5168 pg/ mL; p<0.01). 치료 12개월, 24개월 의 누적 BT 발생률은 HBeAg 양성군에서는 12%, 39%였으며 음성군에서는 0%, 7%로서 음성군에서의 발생율이 양성군에 비하여 낮았다(p<0.01). 다변량 분석으로 확인한 BT와 관계있는 유일한 인자는 HBeAg의 존재 유무였다(p<0.05). YMDD 변이종은 HBeAg 유무에 관계없이 BT가 발생한 모든 예에서 확인할 수 있었으나 BT가 발생하지 않은 경우에서 YMDD 변이종의 발생률은 HBeAg 양성군보다 HBeAg 음성군에서 유의하게 더 높았다(14.3% vs. 50.0%; p<0.01). 결론: HBeAg 음성 만성 B형 간염 환자에서의 라미부딘 치료는 YMDD 변이종이 발생 하여도 BT 발생 빈도가 낮아서 라미부딘의 지속적인 치료효과를 기대해 볼 수 있으리라 생각된다. Background/Aims: Long-term efficacy and the rate of viral breakthrough in patients with HBeAg- negative chronic hepatitis B receiving lamivudine therapy is uncertain. This study was conducted to determine the rate of viral breakthrough according to the HBeAg status and the relation of viral breakthrough with YMDD mutants. Methods: Two hundred and five patients with HBeAg-positive and 49 patients with HBeAg-negative chronic hepatitis B, who had received lamivudine for at least 9 months, were included. The mean durations of the lamivudine treatment were 176 months and 155 months in HBeAg-positive and negative patients, respectively. Analysis of HBV genome for YMDD mutations was performed by restriction-fragment-length polymorphism assay and direct sequencing. Results: While the cumulative rates of viral breakthrough at 12th and 24th months of the lamivudine therapy were 0% and 7% in the HBeAg-negative group, they were 12% and 39% in the HBeAg-positive group. The cumulative rate of viral breakthrough in the HBeAg-negative group was significantly lower than in the HBeAg-positive group (p<0.01). In multivariate analysis, the only significant factor related to viral breakthrough was the HBeAg status (p<0.05). The YMDD mutants were detected in all patients with viral breakthrough irrespective of HBeAg status. However, in patients without viral breakthrough, the rate of YMDD mutants was significantly higher in the HBeAg-negative group than in the HBeAg-positive group (13.3% vs 5.1%; p<0.01). Conclusions: Lamivudine is expected to be more persistently effective in HBeAg-negative chronic hepatitis B because of a lower viral breakthrough rate than in HBeAg-positive chronic hepatitis B in spite of the emergence of YMDD mutants.(Korean J Hepatol 2002;8:397-404)

만성 B형 간염에서 라미부딘 치료중 발생한 Viral Breakthrough 예의 임상 결과

안수현,장윤정,오성남,최도원,백수정,정원석,최창원,김경오,임형준,조남영,박종재,김재선,박영태,이명석,연종은,변관수,이창홍 대한간학회 2002 Clinical and Molecular Hepatology(대한간학회지) Vol.8 No.4

목적: 만성 B형 간염의 치료 중 발생하는 약제 내성 변이종은 임상적으로는 치료 중 음전되었던 혈청 HBV DNA가 다시 양전되는 viral breakthrough 로 진단할 수 있다. 현재 약제 내성 변이종이 발생했을 경우라도 라미부딘 치료를 계속 유지하는 것을 권장하고 있으나, viral breakthrough 발생 예들의 장기적 임상경과가 아직도 불명확하여 이것을 일반화하기는 어려운 상황이다. 이에 라미부딘 사용 중 viral breakthrough 가 발생한 예들을 대상으로 그 임상경과를 알아보고자 하였다. 대상과 방법: 9개월 이상 라미부딘을 투약한 만성 B형 간염 환자로 viral breakthrough가 발생한 74명을 대상으로 하였다(남/여 54/20, 평균연령 42세). Viral breakthrough 후 혈청 ALT치, 총 빌리루빈치, HBV DNA 역가, HBeAg, anti-HBe를 정기적으로 검사하면서 임상경과를 관찰하였다. Viral breakthrough 후 라미부딘의 투약기간은 평균 13개 월(1-41개월)이었다. 결과: Viral breakthrough 발생후 혈청 ALT치가 정상으로 유지되었던 환자는 8예(11%)에 불과했고 나머지 66예(89%)에서는 ALT치가 증가하였으며, 이중 30예(41%)에서 급성 악화(ALT 정상 상한치의 5배 이상 상승)를 보였다. 급성악화는 viral breakthrough 후 3개월 내에 19예 (63%)에서 발생하여 3개월 내에 발생한 예가 많았으나 12개월 이상 지나서 나타나는 예도 약 20%에서 있었다. 비대상성 악화는 6예에서 관찰되었다. Viral breakthrough 후 급성악화가 일어난 예와 없었던 예의 비교에서 급성악화를 예측할 수 있는 인자는 발견할 수 없었다. Viral breakthrough 후 발견할 수 없었다. Viral breakthrough 후 HBeAg이 음전된 예는 8예(11%)였으나 그 임상경과는 양호하지 않았다. 결론: 만성 B형 간염 환자 에서 라미부딘 투여 중 발생한 viral breakthrough 예 중 상당수에서 급성악화가 발생하였으며, HBeAg 이 소실되더라도 그 임상경과는 양호하지만은 않았다. Viral breakthrough 발생 후 주의 깊은 임상경과 의 관찰이 요구되며, 앞으로 viral breakthrough 후 급성악화 예에 대한 대규모 연구와 적절한 치료방향의 제시가 이루어져야 할 것으로 생각된다. Background/Aims: Long-term lamivudine therapy can induce the emergence of lamivudine resistant hepatitis B virus (HBV) mutants. Clinically emergence of the mutant is expressed by the reappearance of disappeared HBV DNA in serum. Continued lamivudine treatment has been usually recommended in cases of viral breakthrough. However, the clinical outcome in patients with viral breakthrough is not clear. The aim of this study was to investigate the clinical course of chronic hepatitis B patients after viral breakthrough during lamivudine therapy. Methods: A total of 74 patients with chronic hepatitis B who showed viral breakthrough after at least 6 months of lamivudine treatment were included in this study. They had positive HBeAg and HBV DNA before treatment. The median follow-up duration after breakthrough was 13 months. Results: After viral breakthrough, only 8 patients (11%) maintained normal ALT levels and 66 patients (89%) showed elevation of ALT. 30 patients (41%) showed acute exacerbation of hepatitis (ALT increase over five-times upper normal limit). These acute exacerbations occurred within three months after breakthrough in 19 patients (63%). In the cases of acute exacerbation, 6 patients showed decompensated progression such as elevation of serum total bilirubin. One of them died of hepatic failure. A predictive factor for acute exacerbation was not found. HBeAg seroconversion occurred in 8 patients after viral breakthrough but their clinical course was highly variable. Conclusions: Chronic hepatitis B patients who had viral breakthrough during lamivudine therapy should be followed carefully and regularly in mind of potential clinical deterioration. New strategies are needed to manage the cases of acute exacerbation after viral breakthrough.(Korean J Hepatol 2002;8:389-396)