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B 형 바이러스성 만성 활동성 간염 환자에서 스테로이드 이탈요법 및 알파 인터페론 투여에 의한 면역상태의 변화
이관식(Kwan Sik Lee),한광협(Kwang Hyub Han),정준표(Jun Pyo Chung),전재윤(Chae Yoon Chon),이상인(Sang In Lee),문영명(Young Myung Moon),강진경(Jin Kyung Kang),박인서(In Suh Park),최흥재(Heung Jai Choi),신전수(Jeon Soo Shin),최인홍(In H 대한내과학회 1995 대한내과학회지 Vol.49 No.1
N/A Objectives: It has been suggested that cellular immune responses to the hepatitis B virus are of importance in the production of liver cell damage in chronic active hepatitis type B. Short-term corticosteroid withdrawal in patients with chronic active hepatitis type B is frequently associated with enhanced cellular immune responses to hepatitis B virus. Several clinical studies had suggested that short-term corticosteroid withdrawal followed by interferon treatment might enhance its antiviral efficacy. The present study was designed to investigate the change of immune parameters in patients with chronic active heptitis type B treatment with short-term corticosteroid withdrawal followed by interferon alpha(IFN-a). Methods: The subjects were 11 patients with chronic active hepatitis type B who were given prednisolone in decreasing daily doses of 60mg, 40mg and 20mg, each for 2 weeks, followed by a 4-week rest and l6 weeks of recombinant alpha 2a interferon (INF-α) was administered intramuscularly. Serum ALT level, serum HBV DNA level and serum sIL-2R level were assayed and CD4+ T cell/ CD8+T cell ratio, IL-2R+T cell/Total T cell(%), TLiSAI+T cell/Total T cell(%) and suppressor T cell activity were measured. Results: 1) The serum ALT level was increased significantly at 2 weeks after the end of prednisolone administration(p<0.005) and decreased significantly after the start of INF-α administration(p<0.005). 2) The serum HBV DNA level was increased significantly during the prednisolone administration(p<0.01) and decreased siginificantly after the end of prednisolone administration and resting period(p<0.05). 3) The serum sIL-2R level was increased significantly at 2 weeks after the end of prednisalone administration(p<0.05). After the end of prednisolone administration and the start of INF-α administration, the serum sIL-2R level was decreased significantly( p<0.05). 4) The increase of serum ALT level after the increase of IL-2R+T cell(%) and TLiSA1+ T cell/ Total T cell(%) after the increase of TLiSA1+T cell/ Total T cell(%) was significant. 5) The maximum increase of serum ALT level and the maximum decrease of suppressor T cell activity were observed in 4 of 5 patients(80.0%) at 2 weeks after the end of prednisolone administration. Conclusion: The serum HBV DNA level was decreased significantly by the immune rebound after the end of steroid administration. Probably increase of IL-2R+T cell/Total T cell(%) and TliSAl+T cell/ Total T cell(%) and decrease of suppresor T cell activity were related to the immune rebound.
( Sunghwan Yoo ),( Hyun Woong Lee ),( Seung Up Kim ),( Sora Kim ),( Hye Young Chang ),( Jung Il Lee ),( Beom Kyung Kim ),( Jun Yong Park ),( Do Young Kim ),( Kwang-hyub Han ),( Kwan Sik Lee ),( Sang H 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: In 96-week results from double-blind, randomized phase III trials, Tenofovir Alafenamide (TAF) continues to be as effective as Tenofovir Disoproxil Fumarate (TDF) with continued improved renal and bone safety. We compared the efficacy and safety of the two drugs in patients with chronic hepatitis B (CHB) for 2 years. Methods: A total of 890 patients with CHB treated with tenofovir alafenamide (TAF, n = 77) or tenofovir disoproxil fumarate (TDF, n = 813) in two tertiary referral centers between November 1, 2017, and December 31, 2017, were analyzed. Eligible patients were aged at least 18 years with chronic HBV infection (with serum HBV DNA concentrations of >2, 000 IU/mL), serum alanine aminotransferase concentrations of greater than 40 U/L and at no more than twenty times the upper limit of normal, and estimated glomerular filtrate rate (eGFR) of at least 50 mL/min (by the Chronic kidney disease epidemiology collaboration). To reduce selection bias and the effect of potential confounders, propensity scores were calculated by logistic regression based on age, gender, diabetes, compensated cirrhosis, and hepatitis B e antigen (HBeAg) status, initial ALT, initial HBV DNA, total bilirubin, albumin, and platelet counts. Differences between the two groups were balanced by a 1:1 PS-matched analysis (TAF, n=77 vs. TDF, n=77). The primary efficacy endpoint was the proportion of patients who had HBV DNA less than 20 IU/mL at week 96; Serum phosphorus, eGFR, and lipid profile were assessed to evaluate the safety. Results: Baseline characteristics were not different between the two groups. Biochemical response (ALT<40 IU/L) rate in TAF and TDF group was 77.9% (60/77) vs 79.2% (61/77) at 1 year, 92.2% (71/77) vs. 89.6% (69/77) at 2 years. Virological response rates (HBV DNA <20IU/mL) was 62.3% (48/77) vs. 66.2% (51/77) at 1 year, 85.7% (66/77) vs. 84.4% (65/77) at 2 years. There were no statistical differences in biochemical and virological response rates. The mean reduction in serum HBV DNA from baseline to 1 and 2 years were similar in TAF and TDF group (-4.7 vs -5.1 and -5.2 vs -5.2 log10IU/mL, P=0.995). HBeAg seroconversion was 21.6% (8/37) vs 8.6% (3/35) at 2 years (P=0.191). A virological breakthrough was not seen in both groups. At year 2, mean change in eGFR was similar in both groups (TAF +4.7 mL/min vs TDF -1.4 mL/min; P=0·121), mean change in phosphorus was also similar in both group (TAF -0.05 mg/dL vs TDF -0.01 mg/dL; P=0·611). Conclusions: In patients with HBeAg positive and negative CHB, the efficacy and safety of TAF were similar to those of TDF at 2 years.
( Young Eun Chon ),( Hana Park ),( Mi Na Kim ),( Yeonjung Ha ),( Joo Ho Lee ),( Seong Gyu Hwang ),( Kyu Sung Rim ),( Beon Kyung Kim ),( Seung Up Kim ),( Sang Hoon Ahn ),( Do Young Kim ),( Kwang-hyub H 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Neutrophil-lymphocyte ratio (NLR) has recently been reported as a predictor of hepatocellular carcinoma (HCC).<sup>1, 2</sup> We aim to investigate whether NLR is a predictor for patients with HCC undergoing transarterial chemoembolization (TACE) and develop a prediction model based upon it. Methods: 1,697 HCC patients undergoing TACE as a first-line therapy were enrolled from two University Hospitals (derivation set n=1316, external validation set n=381). Serum alpha-feto protein (AFP) level, the Barcelona clinic liver cancer (BCLC) stage, Child-Pugh Class, Tumor Response after TACE, and NLR, which were selected as predictors for overall survival (OS) from a multivariate Cox-regression model were incorporated into a 9-point risk prediction model (ABCRN score). The prognostic performance of ABCRN score was assessed in the derivation set and in the validation set. Results: The time-dependent areas under receiver-operating characteristic curves (AUROCs) for OS of ABCRN score at 1-, 3- and 5-years were 0.808, 0.724 and 0.688 in the derivation set, and those were 0.848, 0.662, and 0.717, in the validation set. ABCRN score had the highest AUROCs for OS at 1/3/5 years, compared with ART (0.577/0.505/0.655), ABCR (0.776/0.645/0.600), and SNACOR (0.770/0.662/0.634) scores, respectively, with statistical significances (all P values <0.05 vs. ABCRN score). Patients were stratified into the three risk groups according to ABCRN score (low,0-2; intermediate,3-6; high,7- 9). Patients with high risk group had a significantly higher mortality risk compared to the intermediate (hazard ratio[HR], 2.8; P<0.001) or low-risk group (HR,. 10.7; P<0.001) Conclusions: : Prognostic performance of ABCRN score in patients with HCC treated with TACE was remarkable and it was better compared to conventional scores. This score will help for further guiding future HCC treatment direction.