만성간염 환자의 혈청에서 중합효소연쇄반응을 이용한 HBV DNA 및 HCV RNA 검출소견

박용욱(Yong Uk Park),서강석(Kang Suk Suh),한상우(Sang Woo Han),김신묵(Sin Mook Kim),최성규(Sung Kyu Choi),서순팔(Soon Pal Suh),김세종(Sei Jong Kim) 대한내과학회 1996 대한내과학회지 Vol.50 No.5

N/A Objectives: It is well-known that chronic hepatitis can be caused by hepatitis viral infection, drugs and toxins, inborn errors of metabolism, and autoimmume disease. Hepatitis B (with or without superimposed hepatitis D) and hepatitis C viral infections are known as the common causes of chronic viral hepatitis. Recently there have been several reports that chronic hepatitis and chronic liver disease can be caused by the superinfection or co-infection of HBV and HCV. We detected HBV DNA and HCV RNA in patients with chronic hepatitis using polymerase chain reaction and compared polymerase chain reaction with enzyme immunoassay in evaluating the presence of a superinfection or co-infection of HBV and HCV. Methods : Using sera from 61patients with histologically proven chronic hepatitis (chronic active hepatitis' 51cases, chronic persistent hepatitis: 10cases), we checked the HBV DNA and HCV RNA using polymerase chain reaction. We also checked the HBV and HCV markers using enzyme immunoassay. Results: 1) Only HBV DNA could be detected in 37patients (60.7%). HBV DNA and HCV RNA were detected in 11patients (18%). Only HCV RNA was dectected in 4patients (6.6%). Neither HBV DNA nor HCV RNA was found in 9patients (14.8%). 2) HBV DNA and HCV RNA were detected in 11patients (18%) whereas HBsAg or anti-HBe and anti-HCV were seropositive in 4patients (6.5%). 3) The positive rates of HBsAg and HBV DNA were 83.6% and 78.7%, respectively, and the positive rates of HBV DNA in HBsAg-positive cases and in HBeAg-positive cases were 90.2% and 93.0%, respectively. 4) The positive rates of anti-HCV and HCV RNA were 11.5% and 24.6%, respectively, and the positive rates of HCV RNA in anti-HCV positive cases and in anti-HCV negative eases were 85.7% and 14.8%, respectively. Conclusion: It has been suggested that hepatitis B viral infection is the most common cause of chronic hepatitis in Korea, and that hepatitis C virus might also play an etiological role. In this study, we found that 18% of chronic hepatitis patients were superinfected or co-infected with HHV and HCV, and that polymerase chain reaction was more sensitive than enzyme immunoassay to detect HBV and HCV infection when superinfection or Qo-infection was suspected.

Alcohol Intake and Mortality in Patients with Chronic Viral Hepatitis: A Nationwide Cohort Study

( Dong Hyun Sinn ),( Danbee Kang ),( Eliseo Guallar ),( Yoosoo Chang ),( Seungho Ryu ),( Di Zhao ),( Yun Soo Hong ),( Juhee Cho ),( Geum-youn Gwak ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: We evaluated the association between alcohol intake and all-cause and cause-specific mortality in subjects with chronic viral hepatitis, using nationwide population-based cohort study. Methods: A total of 364,361 men and women 40-84 years of age who underwent health screening exam between January 2002 and December 2013 that included assessment of frequency and amount of alcohol consumption were assessed for all-cause and cause-specific mortality. Results: In participants without chronic viral hepatitis, the fully-adjusted hazard ratios (HR) for all-cause mortality comparing light, moderate, and heavy drinkers to non-drinkers were 0.90 (95% CI 0.85-0.96), 1.06 (95% CI 0.99-1.13), and 1.48 (95% CI 1.30-1.68), respectively. In participants with chronic viral hepatitis, the corresponding HRs were 1.15 (95% CI 1.01-1.30), 1.18 (95% CI 1.01-1.37), and 1.66 (95% CI 1.26-2.20), respectively (P-value for alcohol intake by chronic viral hepatitis interaction <0.001). Compared to participants without chronic viral hepatitis, those with chronic viral hepatitis had substantially elevated liver cancer or liver disease (HR 11.76, 95% CI 10.58-13.07) and extrahepatic cancer mortality (HR 1.41, 95% CI 1.30-1.54). In patients with chronic viral hepatitis, the high mortality due to liver cancer or liver disease and the positive association of alcohol intake with liver cancer or liver disease mortality explained the positive association of alcohol intake with all-cause mortality. Conclusions: Even light to moderate alcohol intake was associated with increased all-cause mortality in individuals with chronic viral hepatitis. Clinicians and public health campaigns should advise against any amount of alcohol intake in individuals with chronic viral hepatitis.

만성간염 환자에서 간 섬유화의 조직학적 활성도 예측에 대한 혈청학적 표지자의 유용성

방창석 ( Chang Seok Bang ),강하얀 ( Ha Yan Kang ),최규호 ( Gyu Ho Choi ),김석배 ( Suk Bae Kim ),이원애 ( Wonae Lee ),송일한 ( Il Han Song ) 대한소화기학회 2017 대한소화기학회지 Vol.69 No.5

Background/Aims: The invasiveness of a liver biopsy and its inconsistent results have prompted efforts to develop noninvasive tools to evaluate the severity of chronic hepatitis. This study was intended to assess the performance of serum biomarkers for predicting liver fibrosis in patients with chronic viral hepatitis. Methods: A total of 302 patients with chronic hepatitis B or C, who had undergone liver biopsy, were retrospectively enrolled. We investigated the diagnostic accuracy of several clinical factors for predicting advanced fibrosis (F≥3). Results: The study population included 227 patients with chronic hepatitis B, 73 patients with chronic hepatitis C, and 2 patients with co-infection (hepatitis B and C). Histological cirrhosis was identified in 16.2% of the study population. The grade of porto-periportal activity was more correlated with the stage of chronic hepatitis compared with that of lobular activity (r=0.640 vs. r=0.171). Fibrosis stage was correlated with platelet count (r=-0.520), aspartate aminotransferase to platelet ratio index (APRI) (r=0.390), prothrombin time (r=0.376), and albumin (r=-0.357). For the diagnosis of advanced fibrosis, platelet count and APRI were the most predictive variables (AUROC=0.752, and 0.713, respectively). Conclusions: In a hepatitis B endemic region, platelet count and APRI could be considered as reliable non-invasive markers for predicting fibrosis of chronic viral hepatitis. However, it is necessary to validate the diagnostic accuracy of these markers in another population. (Korean J Gastroenterol 2017;69:298-307)

비A비B형 만성 간염 환자의 혈청에서 C형 간염 바이러스 RNA의 검출

조성원(Sung Won Cho),심찬섭(Chan Sup Shim),이준성(Joon Seong Lee),김진홍(Jin Hong Kim),이문성(Moon Sung Lee),이희발(Hi Bahl Lee) 대한소화기학회 1993 대한소화기학회지 Vol.25 No.5

N/A Hepatitis C virus is a positive stranded RNA virus which replicates through a negative stranded RNA. To study the role of hepatitis C virus in non-A, non-B chronic hepatitis, serum samples were tested for detection of genomic hepatitis C virus RNA and negative stranded RNA. from 30 patients with non-A, non-B chronic hepatitis using a combination assay of reverse transcription and polymerase chain reaction. Hepatitis C, virus RNA was detected in 28 of 30 patients with non-A, non-B chronic hepatitis. Of these patients, the RNA was detected in 24 of 25 patients positive for antibody to hepatitis C virus and also in 4 of 5 patients negative for antibody to hepatitis C virus. The negative strand was detected in 10 of 30 patients. Of these patients, the negative strand was detected in 9 of 25 patients positive for antibody to hepatitis C virus and in 1 of 5 patients negative for antibody to hepatitis C virus. The presence of the negative strand in serum was not associated with higher serum transaminase levels. These results show that most patients with non-A, non-B chronic hepatitis are infected with hepatitis C virus in Korea, regardless of the presence or absence of antibody to hepatitis C virus.

PCNA Expression and Electron Microscopic Study of Acinus - Forming Hepatocytes in Chronic Hepatitis B

(Nam Ik Han),(Young Sok Lee),(Hwang Choi),(Jong Young Choi),(Seung Kyu Yun),(Se Hyun Cho),(Jun Youl Han),(Jin Mo Yang),(Byung Min Ahn),(Sang Wook Choi),(Chang Don Lee),(Sang Bok Cha),(Hee Sik Sun),(Do 대한내과학회 2002 The Korean Journal of Internal Medicine Vol.17 No.2

N/A Background: One of the major morphologic characteristics of hepatitis B is a hepatocellular regeneration which is induced by massive hepatocyte necrosis and associated with proliferative activity of hepatocytes. The purpose of this study is to document the proliferative activity of hepatocytes in various types of hepatitis B by immunohistochemical staining for proliferative cell nuclear antigen-labelling index (PCNA-LI) and electron microscopy. Methods: We studied 83 patients with hepatitis B; 11 cases of acute viral hepatitis, 24 cases of mild chronic hepatitis, 34 cases of severe chronic hepatitis with early cirrhosis and 14 cases of severe chronic hepatitis. The PCNA was tested by immunohistochemical staining using anti-PCNA antibody. Furthermore we evaluated the ultrastructure of acinus-forming hepatocytes (AFH) by electron microscopy. Results : The expression rate and labelling index of PCNA were 27.3% and 5.3±0.9% in acute viral hepatitis, 62.5% and 22.9 ±31.7% in mild chronic hepatits, and then 47.1% and 14.1± 24.2% in severe chronic hepatitis with early cirrhosis, respectively (Figure 1). By contrast, no detectable PCNA expression was noted in AFH. Electron microscopic findings showed that hepatocytes forming a rosette underwent marked degenerative changes with sinusoidal capillarization and increased fine strands of collagen fiber in portal area. Conclusion: The proliferative acitivity of hepatitis B was significantly decreased in severe chronic hepatitis containing AFH. This result suggested that differences in proliferative activity was associated with hepatic cell necrosis and AFH.

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 B형 간염 환자의 간 생검 소견과 HBsAg 및 HBcAg 발현 양상 관계

강대영,최정목 충남대학교 의과대학 지역사회의학연구소 1994 충남의대잡지 Vol.21 No.2

To elucidate the significance of HBsAg and HBcAg expression patterns in the liver, 36 cases of chronic hepatitis(19 CAH, 16CPH) were studied by immunohistochemical method and clinical laboratory data such as GOT and GPT. The results were as follows ; 1. With immunohistochemical staining, HBcAg was expressed in the 25 out of 36 cases(69.4%), and HBsAg was expressed in the total cases(100.0%) 2. The incidence of cytoplasmic HBcAg expression in chronic active hepatitis(15 cases; 78.9%) was similar to that. of nuclear HBcAg(12 cases, 63.2%), whereas that of chronic perisistent hepatitis was higher in the nucleus(58.9%) than in the cytoplasm (29.4%). 3. With tissue expression pattern of HBcAg and HBsAg according to pathological diagnosis, the pattern IV was predominant in the chronic active hepatitis (63.2%), whereas the pattern II(47.1%) and III(35.3%) were predominant in the chronic perisistent hepatitis. 4. The high serum transaminase levels was coincided with the decreasing nuclear HBcAg expression and with the increasing cytoplasmic HBcAg expression. The results suggest that expression of HBcAg correlates with prognosis of chronic hepatitis B virus infection.

혈청 제4형 콜라겐 7S Domain 측정에 의한 만성 간염의 섬유화 정도 예측

이계희(Kye Heui Lee),박성훈(Seong Hoon Park),최신은(Shin Eun Choi),김안나(An Na Kim),김성용(sung Yong Kim),임선희(Sun Hee Lim),임용성(Yong Sung Lim),손인(In Son) 대한소화기학회 1993 대한소화기학회지 Vol.25 No.2

N/A The degree of fibrosis is a major prognostic factor in chronic liver disease. Although liver biopsy is essential to assess the degree of fibrosis, a more simple diagnostic method would be helpful for its invasive nature. Type IV collagen is one of major constituents of basement membrane and serum collagen IV-7S level reflects the degree of fibrosis. To evaluate the usefulness of serum collagen IV-7S in assessing the state of hepatic fibrosis, we compared the level of serum collagen IV-7S in various liver diseases and normal volunteers. The normal value of the serum collagen IV-7S was 3.6+- 1.2 ng/ml. There was no statistically significant difference in serum collagen IV-7S levels among the group of acute hepatitis, fatty liver, chronic persistent hepatitis and the normal controls. And there was no significant difference between the group of chronic active hepatitis and liver cirrhosis, either. But the level of serum collagen IV-7S of the group of chronic active hepatitis and liver cirrhosis was significantly higher than that of the group of acute viral hepatitis, fatty liver and chronic persistent hepatitis. These results suggest that the measurement of serum collagen IV-7S is a valuable aid for evaluating the state of fibrrosis in chronic liver disease.

소아 만성 B형 간염 환자에서 스테로이드 이탈 요법 후 인터페론 병용 투여의 치료 효과

류나은,김병주,마재숙,황태주,Ryu, Na-Eun,Kim, Byung-Ju,Ma, Jae-Sook,Hwang, Tai-Ju 대한소아소화기영양학회 1999 Pediatric gastroenterology, hepatology & nutrition Vol.2 No.2

목 적: 소아 만성 B형 간염 환아에서 알파 인터페론의 치료 효과는 보고자마다 차이가 있으나 30~40%로 알려져 있다. 그러나 만성 지속성 B형 간염, 혈청 ALT치가 낮은 경우나 혈청 HBV DNA치가 높은 소아 만성 B형 간염 환자에서 알파 인터페론 단독 투여 시 그 치료 효과는 더 낮다고 보고되고 있다. 이에 저자들은 알파 인터페론 단독 투여 시 치료 효과가 낮다고 알려진 소아 만성 B형간염 환자에 prednisolone 이탈 요법 후 인터페론 병용 투여 시 그 치료 효과를 알아보고자 본 연구를 시행하였다. 대상 및 방법: 1996년 1월부터 1997년 12월까지 전남대학교병원 소아과에 내원하여 만성 B형 간염으로 진단받은 28명을 대상으로 하였다. 대상 환아 중 간 조직 검사 상 만성 활동성 간염을 보이고 혈청 ALT치가 100 IU/L 이상이고 혈청 HBV-DNA치가 100 pg/$300\;{\mu}L$ 미만인 14명(group 1)은 알파 인터페론을 체표면적($m^2$) 당 5백만 단위를 6개월 동안 주 3회 단독 투여하였다. 조직 검사 상 만성 지속성 간염인 경우와 만성 활동성 간염이면서 혈청ALT치가 100 IU/L 미만 또는 혈청 HBV DNA치가 100 pg/$300\;{\mu}L$ 초과한 14명(group 2)은 prednisolone을 60 mg/$m^2$, 40 mg/$m^2$, 20 mg/$m^2$으로 각각 2주씩 6주간 경구 투여하고 2주간 휴약 기간을 가진 후 알파 인터페론을 group 1과 같은 방법으로 투여하였다. 치료에 대한 반응은 인터페론 투여가 종료되는 시점에서 완전반응(항 HBe 항체의 양전화, 혈청 ALT 정상화 및 혈청 HBV-DNA 음성), 부분반응(혈청 ALT 정상화 또는 혈청 HBV-DNA 음성) 및 무반응으로 평가하였다. 결 과: 1) 대상 환아의 평균 연령은 130.6개월(21~192개월)이었고, 남아는 22례, 여아는 6례이었다. 만성 지속성 간염은 11례, 만성 활동성 간염은 17례이었고, 15명의 환아에서 모친이 B형 간염 바이러스 만성 보유자이었다. 2) Group 1에서 평균 연령은 144.1개월(97~169개월), 남아 9명, 여아 5명, 혈청 ALT $299.9{\pm}215.3$ IU/L, HBV-DNA $49.3{\pm}33.1\;pg/300\;{\mu}L$이었고, group 2에서 평균 연령은 112.1개월(21~192개월), 남아 13명, 여아 1명, 만성 지속성 간염 11명, 만성 활동성 간염 3명, 혈청 ALT $85.6{\pm}71.0$ IU/L, HBVDNA $524.3{\pm}1064\;pg/300\;{\mu}L$이었다. 3) Group 1에서 항 HBe 항체 양전은 10례(71.4%) 에서, 혈청 ALT는 9례(64.3%)에서 정상화되었고, HBV-DNA는 11례(78.6%)에서 음성화되었다. Group 2에서 항 HBe 항체 양전은 7례(50.0%)에서, 비정상 수치를 보인 9명의 환아 중 5명(55.6%)이 ALT 의 정상화를 보였고, HBV-DNA는 9례(64.3%)에서 음성화되었다. 두 군간의 항 HBe 항체의 양전율, ALT치의 정상화율, HBV DNA치의 음성화율에 있어서 통계학적으로 유의한 차이는 없었다. 4) Group 1에서 완전반응은 8례(57.1%), 부분반응은 3례(21.4%), 무반응은 3례(21.4%)이었고, group 2 에서는 완전반응 7례(50.0%), 부분반응 2례(14.3%), 무반응 5례(35.7%)으로 두 군간의 통계학적 유의한 차이는 없었다. 결 론: 소아 만성 B형 간염에 대한 치료로 인터페론 단독 요법으로 반응이 좋지 않을 것으로 예측되는 환자군에 스테로이드 이탈 요법 후 인터페론 병합 투여는 안전하고 효과적인 치료법으로 생각된다. 향후 치료 효과의 지속 여부에 대한 지속적인 관찰과 더 많은 환자를 대상으로 한 전향적인 비교 연구가 필요하리라 사료된다. Purpose: To evaluate the efficacy of interferon alpha therapy with or without prednisolone in children with chronic hepatitis B. Methods: Twenty-eight children (22 boys, 6 girls, mean age 130 months) had seropositive results for HBsAg, HBeAg and HBV DNA; 11 had chronic persistent hepatitis and 17 had chronic active hepatitis. The patients were divided into two groups depending upon their inflammatory activity on liver biopsy, pretreatment serum ALT levels and HBV DNA levels. Fourteen children (group 1: chronic active hepatitis, ALT ${\geq}$ 100 IU/L and HBV DNA ${\leq}$ 100 pg/$300\;{\mu}L$) received interferon alpha 2a 5 $MU/m^2$ of body surface three times weekly for 6 months. Fourteen children (group 2: chronic persistent hepatitis or chronic active hepatitis with ALT < 100 IU/L or HBV DNA > 100 pg/$300\;{\mu}L$) received prednisolone in decreasing daily doses of 60 mg/$m^2$, 40 mg/$m^2$, and 20 mg/$m^2$, each for 2 weeks, followed after 2 weeks by interferon alpha 2a on the same schedule. At the end of therapy, 3 end points were analyzed: HBeAg seroconversion, serum ALT normalization rate and clearance of serum HBV DNA. Results: At the end of treatment, HBe antigen-to antibody seroconversion was higher but not more significant in group 1 than group 2 (71.4% vs. 50.0%). Only one patient in group 2 who lost HBeAg, also cleared HBsAg. ALT normalization was similar in both groups (64.3% in group 1 vs. 55.6% in group 2). Clearance of serum HBV DNA was observed in 78.6% of patients in group 1 and 64.3% in group 2, but no significant differences. Complete response was similarly achieved in both groups (57.1% in group 1 vs. 50.0% in group 2). Interferon alpha therapy with prednisolone priming was well tolerated and all children finished therapy. Conclusion: The combined therapy with prednisolone followed by interferon alpha may be safe and effective in inducing a serological and biochemical remission of the disease in approximately 50% of children with chronic hepatitis B and with a high level of viral replication and less active disease. However, a controlled study should be performed to confirm these results.

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.