• Molecules and Cells
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• 제37권1호
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• pp.66-73
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• 2014

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.

• Pediatric Infection and Vaccine
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• 제11권1호
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• pp.73-80
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• 2004

목 적 : 소아 HBV 만성 감염 환자들에 대한 연속적인 임상적 소견, 생화학 검사 및 혈청학적 표지자의 변화를 분석하여 이들간의 연관성을 알아보았다. 방 법 : 1995년 7월 1일부터 2000년 6월 30일까지 5년간 가톨릭대학교 성빈센트병원 소아과를 방문하여 6개월 이상 추적이 가능하였던 HBV 만성감염 소아 90명을 대상으로 하였다. 이들 모두는 HBV 표지자인 HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc IgG와 간기능 검사를 시행하였다. 결 과 : 첫 내원시 대상 모두가 무증상이었고 HBV 만성 감염의 가족력이 83%에서 있었다. HBeAg 양성이 81%, HBeAg 음성, anti-HBe 양성이 16%, HBeAg, anti-HBe 모두 음성인 경우가 3%로 성별간의 차이는 없었고, 대상군의 연령을 0~5, 6~10, 11~15세로 나누었을 때 HBeAg 양성은 각각 90%, 96%, 61%로 10세 이하의 양성률이 11~15세에 비해 의미있게 높았다(P=0.001). 혈청 ALT치는 40 IU/L 이하, 41~80 IU/L, 81~200 IU/L, 201 IU 이상인 경우가 각각 64%, 17%, 10%, 9%이었고 HBeAg 양성군이 음성군에 비해 ALT의 비정상인 경우가 의미있게 많았다(P=0.036). HBeAg에서 anti-HBe로 전환된 경우가 73명 중 11명에서 발생하였고 이들 모두에서 anti-HBe의 전환 전에 ALT치의 증가가 관찰되었다. HBeAg 및 HBsAg의 연간 자연소실율은 각각 9.7%, 0.6%이었다. 결 론 : HBV 표지자 및 생화학적 검사치의 변화양상을 숙지하는 것은 이와 관련된 연구를 시행할 때 대상을 선정하고 또한 질환에 대한 치료 여부, 치료제의 선택 및 효과를 검토할 때 필요한 사항이며 각 개인의 HBV 만성 감염의 악화 예후인자를 찾기 위하여 증상이 없더라도 보유자에 대한 계속적인 관찰은 매우 중요하다고 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7825-7829
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• 2015

Background: Egypt has the highest prevalence of HCV infection in the world (~14.7%). Around 10-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. The incidence of HCC is expected to grow in the next two decades, largely due to HCV related cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. No simple reliable non-invasive marker has been available till now. B2M, a non-glycosylated polypeptide composed of 99 amino acids, is one of the components of HLA class I molecules on the surfaces of all nucleated cells. It has been reported that the level of serum B2M is elevated in patients with chronic hepatitis C and HCV-related HCC when compared to HCV-negative patients or healthy donors. Determining the clinical utility of serum B2M as a marker for disease progression in Egyptian patients with HCV related chronic hepatitis, cirrhosis and hepatocellular carcinoma was the aim of the present study. Materials and Methods: In this analytical cross sectional study 92 participants were included in 4 equal groups: Group (1) non cirrhotic chronic HCV; Group (2) HCV related liver cirrhosis; Group (3) HCC on top of HCV,; and Group (4) healthy controls. History taking, clinical examination, routine labs and abdominal ultrasound were conducted for all patients, PCR and Metavir scores for group (1) patients, and triphasic CT abdomen and AFP for Group (3) patients. B2M levels were measured in serum with a fully-automated IMX system. Results: The mean serum B2M level of Group (1) was $4.25{\pm}1.48{\mu}g/ml$., Group (2) was $7.48{\pm}3.04$, Group (3) was $6.62{\pm}2.49$ and Group (4) was $1.62{\pm}0.63$. Serum B2M levels were significantly higher in diseased than control group (p<0.01) being significantly higher in cirrhosis ($7.48{\pm}3.04$) and HCC groups ($6.62{\pm}2.49$) than the HCV group ($4.25{\pm}1.48$) (p<0.01). There was a significant correlation between B2M Level and ALK, total and direct bilirubin and INR (p<0.05), and a significant inverse correlation between B2M level and albumin, total proteins, HB andWBCS values (p<0.05). There was no significant correlation between B2M level and viral load or Metavir score, largest tumour size or AFP (p>0.05). The best B2M cut-off for HCV diagnosis was 2.6 with a sensitivity of 100%, a specificity of 92%, a positive predictive value (PPV) of 97% and a negative predictive value (NPV) of 100%. The best B2M cut-off for HCC diagnosis was 4.55 which yielded sensitivity, specificity, positive predictive value, negative predictive values of 74%, 62%, 39.5, 87.8% respectively (p-value <0.01) while best cut-off for cirrhosis was 4.9, with sensitivity 74 % and specificity 74%.The sensitivity for HCC diagnosis increased upon B2M and AFP combined estimation to 91%, specificity to 79%, NPV to 95% and accuracy to 83%. Conclusions: Serum B2M level is elevated in HCV related chronic liver diseases and may be used as a marker for HCV disease progression towards cirrhosis and carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2923-2927
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• 2014

Background: Hepatocellular cancer (HCC) is one of the important health problems in Turkey, being very common and highly lethal. The aim of this study was to determine clinical, demographic features and risk factors. Materials and Methods: Nine hundred and sixth-three patients with HCC from 13 cities in Turkey were included in this study. Results: Only 205 (21%) of the 963 patients were women, with a male:female predominance of 4.8:1 and a median age of 61 years. The etiologic risk factors for HCC were hepatitis B in 555 patients (57.6%), 453 (81%) in men, and 102 (19%) in women, again with male predominance, hepatitis C in 159 (16.5%), (14.9% and 22.4%, with a higher incidence in women), and chronic alcohol abuse (more than ten years) in 137 (14.2%) (16.8% and 4.9%, higher in males). The Child-Pugh score paralleled with advanced disease stage amd also a high level of AFP. Conclusions: According to our findings the viral etiology (hepatitis B and hepatitis C infections) in the Turkish population was the most important factor in HCC development, with alcohol abuse as the third risk factor. The Child-Pugh classification and AFP levels were determined to be important prognostic factors in HCC patients.

• Journal of Yeungnam Medical Science
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• 제36권2호
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• pp.67-77
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• 2019

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.

• 대한한의학회지
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• 제19권2호
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• pp.244-270
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• 1998

This study was performed to investigate an anti-HBV activities of the aqueous extracts from 10 Korean herbal medicines in the HepG2 2.2.15 cell culture system and the results were as follows: 1. The extracts of 6 plants (Herba Artemisiae Capillaris, Radix et Rhizoma Rhei, Cortex Cinnamomi, Fructus Chebulae, Fructus Rubi and Radix Rubi) decreased, significantly and dose-dependently, the levels of extracellular HBV virion in the concentrations (10, 100, 500 and $1,000\;{\mu}g/m{\ell}$) tested. 2. However, others (Radix lsatidis, Lignum Sappan, Herba Lysimachiae and Fructus Lycii) did not show any effect either on the replication of HBV or on the levels of virion DNA in the culture media of HepG2 2.2.15 cell. 3. Among the 6 plants which showed the inhibitory potency on the production of extracellular HBV virion, Radix et Rhizoma Rhei, Cortex Cinnamomi, Fructus Chebulae, Fructus Rubi and Radix Rubi except Herba Artemisiae Capillaris also showed the inhibition of the replication of intracellular HEV DNA in the range of $100{\sim}500\;{\mu}g/m{\ell}$. Considering the above results, it is thought that 6 plants(Herba Artemisiae Capillaris, Radix et Rhizoma Rhei, Cortex Cinnamomi, Fructus Chebulae, Fructus Rubi and Radix Rubi) possess the anti-HBV activities in the HepG2 2.2.15 cell culture system. We thus suggest that these plants possess a potential as a therapeutic agent for the chronic viral hepatitis. These results might be useful as a basic data for the development of the new preventive drugs for HBV diseases.

• Journal of Chest Surgery
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• 제31권4호
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• pp.393-397
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• 1998

25세된 말기 심부전 환자에게 한국에서는 최초로 광배근을 이용한 심근 성형술이 성공적으로 실시되었다. 환자는 약 심근수축력이 30%인 상태로 94년과 96년에 한차례씩 심부전으로 입원한 적이 있으며 수술직전 임상상태는 NYHA functional class III 였다. 간조직 검사상 만성 활동성 간염으로 판명되었으며 환자는 간염 항원이 양성으로 심장이식대상에서 제외되었다. 1996년 7월 30일 좌측 광배근을 이용하여 심근 성형술을 실시하였다. 측와위로 광배근을 박리한후 자극전극을 설치하였으며 흉골 정중 절개로 심장을 노출한 후 광배근으로 심장을 감싸주고 심근 전극을 설치한 후 좌상부 복부에 심장근육자극기를 설치하였다. 총 수술시간은 약 7시간 30분이 소요되었으며 환자는 수술후 일시적인 심방 조동(atrial flutter)을 보여 심도자실에서 동율동으로 환원시킨 것외에는 특별한 합병증은 없었다. 환자는 수술후 6주째 자극기의 빈도가 1:4인 상태에서 퇴원하였으며 통원치료중 1:1로 근육훈련을 마친 후 현재는 수술후 6개월째 자극빈도가 1:4인 상태에서 외래 추적중이다. 심초음파상 수축력의 차이는 없으나 환자의 임상 활동은 수술전보다 양호해진 상태이다.

• Clinical and Experimental Pediatrics
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• 제50권4호
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• pp.348-354
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• 2007

목 적 : B형 간염 바이러스 주산기 감염은 현재 감소하고 있지만 HBeAg 양성 산모로부터 분만된 신생아의 10%는 예방조치에도 불구하고 보유자가 된다. 비록 예방조치 실패의 원인이 아직 불확실하나 산모의 분만시 HBV-DNA 수치의 중요성이 제시되고 있다. 본 연구는 산모의 분만시 HBV-DNA 수치가 주산기 예방조치 결과의 유용한 예측인자임을 확인하기 위하여 시행하였다. 방 법 : 주산기 예방조치의 결과를 이미 알고 있는 29명의 HBeAg 양성 산모를 선정하였다. 산모의 HBV-DNA 양을 측정하기 위하여 WHO International Standard For Hepatitis B Virus DNA For NAT Assay를 이용한 정량적 PCR을 시행하였다. 결 과 : 주산기 예방조치 실패군 산모의 로그 HBV-DNA 수치가 성공군 산모의 수치보다 유의하게 높았다(7.99 vs. 6.72, P=0.015). 주산기 예방조치 결과를 예측할 수 있는 산모의 HBV-DNA 수치의 기준은 $2.83{\times}10^7$ 개체/mL(100 pg/mL)로 정할 수 있었는데, 산모의 HBV-DNA 수치가 기준치 미만인 16명 중 예방조치에 실패한 경우는 없었으며(0%), 기준치 이상인 경우는 13명 중 5명(38.5%)이 실패하였다. 결 론 : 현재의 예방조치법으로는 분만시 높은 HBV-DNA 수치를 가지는 산모의 주산기 예방조치 결과는 좋지 않을 가능성이 높다. 따라서 주산기 예방조치의 실패율을 낮추기 위해서는 이러한 위험요인이 있는 경우에 보다 강력한 방법을 적용시켜야 하겠다.

• 생명과학회지
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• 제32권2호
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• pp.94-100
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• 2022

B형간염바이러스(HBV)의 만성 감염은 간경화와 간세포암 발생 빈도를 현저히 높인다. HBV 감염의 임상적 결과는 숙주 유전적 요인과 바이러스의 유전자 변이, 그리고 환경적 요인 등에 결정된다. HBV 복제를 위한 HBV의 pre-genomic RNA 전사는 바이러스의 core promoter 활성화에 의해 조절된다. Core promoter 돌연변이는 급성간 질환과 간세포암 발생에 연관되어 있다. 본 연구팀은 미얀마의 HBV 감염 환자들로부터 바이러스 유전자를 획득하여 core promoter 부위의 유전자 변이들을 파악하였다. Core promoter의 상대적 유전자 활성 차이를 분석하기 위해서 core promoter를 luciferase reporter에 재조합한 시스템을 제작하였다. 분석한 core promoter의 유전자 변이들 중에서 C1731T와 G1806A 돌연변이가 HBV core promoter의 전사 활성화를 증가에 관여하였다. 돌연변이 부위를 중심으로 전사 인자들의 가능한 결합 부위 변화를 컴퓨터 프로그램 분석을 통해 조사한 결과, C/EBPβ와 XBP1 반응 부위가 새롭게 생성되었음을 도출하였다. C/EBPβ의 세포 내 발현은 C1713T 돌연변이를 가진 core promoter의 전사 활성을 증가시켰으며, XBP1 발현은 G1806A 돌연변이를 함유한 M95 promoter를 활성을 증가시켰다. HBV 감염의 치료는 약제 내성과 백신 회피 돌연변이 발생으로 문제점을 가지고 있는 상황에서, 이 연구 결과는 HBV core promoter 돌연변이의 분자생물학적 그리고 임상학적 중요성을 제공한다.