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Hepatitis B surface antigen and hepatitis B core-related antigen kinetics after adding pegylated-interferon to nucleos(t)ids analogues in hepatitis B e antigen-negative patients

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World Journal of Hepatology 2020年第11期12卷 1076-1088页

作者： Teresa Broquetas montserrat garcia-retortillo Miquel Mico Lidia Canillas Marc Puigvehi Nuria Canete Susana Coll Ana Viu Juan Jose Hernandez Xavier Bessa JoseA Carrion Department of Gastroenterology Liver SectionHospital del Mar Medical Research InstituteBarcelona 08003Spain Departament of de Medicina Universitat Autònoma de BarcelonaBarcelona 08003Spain Laboratori de Referencia de Catalunya El Prat de LlobregatBarcelona 08820Spain

BACKGROUND Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues(NAs)rarely achieve hepatitis B surface antigen(HBsAg)loss.AIM To evaluate if the addition of pegylated interferon(Peg-IFN)could decrease HBsAg and hepatitis B core-related antigen(HBcrAg)levels and increase HBsAg loss rate in patients under NAs therapy.METHODS Prospective,non-randomized,open-label trial evaluating the combination of Peg-IFN 180μg/week plus NAs during forty-eight weeks vs NAs in monotherapy.Hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients of a tertiary hospital,under NAs therapy for at least 2 years and with undetectable viral load,were eligible.Patients with hepatitis C virus,hepatitis D virus or human immunodeficiency virus co-infection and liver transplanted patients were excluded.HBsAg and HBcrAg levels(log10 U/mL)were measured at baseline and during ninety-six weeks.HBsAg loss rate was evaluated in both groups.Adverse events were recorded in both groups.The kinetic of HBsAg for each treatment group was evaluated from baseline to weeks 24 and 48 by the slope of the HBsAg decline(log10 IU/mL/week)using a linear regression model.RESULTS Sixty-five patients were enrolled,61%receiving tenofovir and 33%entecavir.Thirty-six(55%)were included in Peg-IFN-NA group and 29(44%)in NA group.After matching by age and treatment duration,baseline HBsAg levels were comparable between groups(3.1 vs 3.2)(P=0.25).HBsAg levels at weeks 24,48 and 96 declined in Peg-IFN-NA group(-0.26,-0.40 and-0.44)and remained stable in NA group(-0.10,-0.10 and-0.10)(P<0.05).The slope of HBsAg decline in Peg-IFN-NA group(-0.02)was higher than in NA group(-0.00)(P=0.015).HBcrAg levels did not change.Eight(22%)patients discontinued Peg-IFN due to adverse events.The HBsAg loss was achieved in 3(8.3%)patients of the Peg-IFN-NA group and 0(0%)of the NA group.CONCLUSION The addition of Peg-IFN to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy.Side effects of Peg-IFN can limit its

关键词： Chronic hepatitis B Hepatitis B e antigen-negative Hepatitis B surface antigen Hepatitis B core-related antigen Pegylated-interferon Nucleos(t)ids analogues©The Author(s)2020.Published by Baishideng Publishing Group Inc.All rights reserved

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通过肝移植过程中的病毒动力学特征研究丙型肝炎次级病毒复制区

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世界核心医学期刊文摘（胃肠病学分册） 2005年第8期1卷 59-59页

作者： Dahari H Feliu A garcia-retortillo M A.U. Neumann 陈瑜 Faculty of Life Sciences Bar-Ilan University 52900 Ramat-Gan Israel

Background/Aims: The existence of an extrahepatic hepatitis C virus replicatio n compartment is an important question for optimizing therapy and preventing the infection of liver grafts.An extraheptic replication compartment could be indic ated if viral decline during the anhepatic phase is not a single exponential.How ever, the duration of the anhepatic phase is too short (0.5-2 h) to allow such analysis. Here we mathematically analyze viral decline during liver transplantat ion beyond the period of the anhepatic phase and examine the possibility of vira l compartmentalization. Methods: Viral load of 30 patients undergoing liver tran splantation was frequently measured. Simulation and non-linear fitting of diffe rential equation models were used to test different compartmentalization hypothe ses.Results: In 16 of the patients (56%), a bi-phasic viral decline was observ ed which is explained by the existence of a second replication compartment. This extrahepatic compartment is responsible for about 3.1%of virus in circulation and the mean half-life of its infected cells is 2.6 days. The remaining patient s, with a single exponential decline, have either a second compartment with rela tively low contribution or no second compartment. Conclusions: These results pro vide a first quantitative picture of the extrahepatic hepatitis C viral contribu tion and may suggest new approaches for viral clearance.

关键词：肝移植病毒复制丙型肝炎力学特征无肝期肝炎病毒单指数病毒数量病毒载量时间太短

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与尸体肝移植相比活体肝移植后患者丙型肝炎的复发更为严重

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世界核心医学期刊文摘（胃肠病学分册） 2005年第2期1卷 42-42页

作者： garcia-retortillo M. Forns X. Llovet J.M. 樊菁 Liver Unit I nstitut de Malalties Digestives Hospital Clinic Villarroel 170 Barcelona 080 36 SpainDr.

Preliminary reports suggested that hepatitis C virus (HCV) infection has a mor e aggressive course following living donor liver transplantation (LDLT) compared to cadaveric liver transplantation (CLT). The aim of this prospective study was to establish if HCV disease recurrence differs between LDLT and CLT. A cohort o f 116 consecutive HCV-infected patients undergoing 117 LTs in a single center f rom March 2000 to August 2003 were followed-up, including systematic liver biop sies. Severe recurrence (SR) was defined as biopsy-proven cirrhosis and/or the occurrence of clinical decompensation. After a median follow-up of 22 months (2 .6-44months), 26 (22%) patients developed SR(decompensation in 12), involving 17 (18%) of 95 patients undergoing CLT and 9 (41%) of 22 undergoing LDLT. The 2-year probability of presenting SR was significantly higher in LDLT compared t o CLT (45%vs. 22%, P = .019). By univariate analysis LDLT (P = .019) and an AL T higher than 80 IU/L 3 months after LT (P = .022) were predictors of SR. In 93 patients from whom a liver biopsy was available 3 months after LT, a lobular nec roinflammatory score > 1 (P >, = 2.8; 95%CI, 1.19-6.6; P = .024) a nd a lobular necroinflammatory score > 1 (OR, 3.1; 95%CI, 1.2-8; P = .013). In conclusion, HCV recurrence is more severe in LDLT compared to CLT. Although our results were based on a single-center experience, they should be considered in the decision-making process of transplant programs, since severe HCV recurrenc emay ultimately compromise graft and patient survival.

关键词：活体肝移植丙型肝炎胆管并发症移植术侵袭力移植物评定过程单变量分析单中心

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