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Kwangrae Cho,Byung-Kwan Chu,Il-Yong Han,Chee-Mahn Shin,김영재,Soon Ho Cheong,이근무,Se Hun Lim,이정한,Myoung-Hun Kim,Hyo-Joong Kim 대한마취통증의학회 2012 Korean Journal of Anesthesiology Vol.62 No.4
Intraoperative formation and management of a thrombus in right atrium has been reported occasionally. Nevertheless, it is rare that a right atrial thrombus with unstable hemodynamic changes detected by transesophageal echocardiography is resolved spontaneously. We report upon the 44-year-old woman, who had a right atrial thrombus detected by transesophageal echocardiography during laparoscopic assisted vaginal hysterectomy and resolved during thromboembolectomy.
( Geum-youn Gwak ),( Young-suk Lim ),( Kwan Soo Byun ),( Yoon Jun Kim ),( Byung Chul Yoo ),( So Young Kwon ),( Jonggi Choi ),( Jihyun An ),( Han Chu Lee ),( Yung Sang Lee ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks displayed non-inferior efficacy to TDF plus entecavir (ETV) combination therapy in hepatitis B virus (HBV) patients resistant to ETV and lamivudine (LAM). However, whether prolonged TDF monotherapy would be safe and increase the virologic response rate in these patients is unclear. Methods: Among 90 patients with HBV resistant to ETV and LAM who were randomized to receive TDF monotherapy (n=45) or TDF/ETV combination therapy (n=45) for 48 weeks, 89 agreed to continue the study on TDF monotherapy, and 84 (93.3%) completed 144 weeks. Results: At baseline, all patients had various HBV mutations resistant to ETV and LAM (rtT184A/C/F/G/I/L/S, rtS202G, and rtM250L/V, in addition to rtM204V/I). By intention-to-treat analysis, 71.1% in the TDF-TDF group and 73.3% in the TDF/ETV-TDF group had serum HBV DNA <15 IU/mL at week 48 (P=0.81). At week 144, the proportion increased to 82.2% and 88.9%, respectively (P=0.37). By on-treatment analysis, 95.1% and 93.0%, respectively, had HBV DNA < 60 IU/mL at week 144 (P=0.68). Virologic breakthrough occurred in 2 patients in TDF-TDF group at week 48 and 120 due to poor drug adherence. At week 144, 5 patients who had HBV DNA >60 IU/mL qualified for HBV genotypic resistance tests, and 2 patients retained some of their baseline resistance mutations. No patients developed additional resistance mutations throughout the study period. Treatment was generally well tolerated. The mean change in estimated GFR from baseline was not significant at week 144 (2.07 mL/min/1.73 m2, P=0.18). The mean change in bone mineral density from baseline at week 144 was 0.32% at spine (P=0.59) and -0.92% at femur (P=0.02). Conclusions: TDF monotherapy was safe and efficacious in patients with ETV-resistant HBV for up to 144 weeks.
( So Young Kwon ),( Young-suk Lim ),( Byung Chul Yoo ),( Kwan Soo Byun ),( Geum-youn Gwak ),( Yoon Jun Kim ),( Jihyun An ),( Han Chu Lee ),( Yung Sang Lee ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: Combination therapy with a nucleoside analogue and a nucleotideanalogue has been generally recommended for the treatmentof patients harboring multiple drug-resistant (MDR) hepatitis B virus(HBV). Little data are available regarding whether switching the combinationtherapy to tenofovir disoproxil fumarate (TDF) monotherapyis safe and efficacious in patients with MDR HBV.Methods: This integrated analysis combines results from two Phase4 trials for 192 patients with HBV resistant to entecavir and adefovir,respectively. In both studies, patients with serum HBV DNA levels>60 IU/mL were randomized to receive TDF (300 mg/day) monotherapy(n=95) or TDF and entecavir (1 mg/day) combination therapy(TDF+ETV, n=97) for 48 weeks. All who completed 48 weeks in eithergroup received TDF monotherapy for 48 additional weeks.Results: Mean basal HBV DNA level was 4.08 log10 IU/mL withoutsignificant difference between TDF and TDF+ETV groups. All patientshad HBV resistance mutations to entecavir and/or adefovir in additionto lamivudine; rtT184A/C/F/G/I/L/S (n=73), rtS202G (n=64), rtM250L/V(n=17), rtA181V/T (n=97), rtN236T (n=39), rtL180M (n=157), andrtM204V/I (n=192). Sixty-eight and 34 patients, respectively, had single(rtA181V/T or rtN236T) and double (rtA181V/T and rtN236T) resistancemutations to adefovir at baseline. The proportion of patientswith HBV DNA <15 IU/mL was not significantly different betweenthe TDF and TDF+ETV groups at week 48 (66.3% vs 68.0%; p=0.80).At week 96, HBV DNA was detectable in 63 patients (32.8%), butthe level was below 3 log10 IU/mL (1.88±0.46 log10 IU/mL) in 62patients. None developed additional resistance mutations.None developedadditional resistance mutations. After switching TDF+ETV toTDF, virologic breakthrough occurred only in one patient at 96 weeksby poor drug adherence. Only higher HBV DNA level (OR, 0.46;P<0.001) and harboring double adefovir-resistance mutations (OR,0.16; P=0.003) at baseline were significantly associated with lowerrate of virologic response at 96 weeks by multivariable analysis.Conclusions: In patients with MDR HBV, TDF monotherapy provideda virologic response comparable to that of TDF+ETV combinationtherapy during 48 weeks of treatment. Switching TDF+ETV combinationtherapy to TDF monotherapy was safe and efficacious.
Lim, Young-Suk,Gwak, Geum-Youn,Choi, Jonggi,Lee, Yung Sang,Byun, Kwan Soo,Kim, Yoon Jun,Yoo, Byung Chul,Kwon, So Young,Lee, Han Chu Elsevier 2019 Journal of hepatology Vol.71 No.1
<P><B>Background & Aims</B></P> <P>Tenofovir disoproxil fumarate (TDF) monotherapy has displayed non-inferior efficacy to TDF plus entecavir (ETV) combination therapy in patients with hepatitis B virus (HBV) resistant to ETV and/or adefovir (ADV). Nonetheless, the virologic response rate was suboptimal in patients receiving up to 144 weeks of TDF monotherapy. We aimed to assess the efficacy and safety of TDF monotherapy given for up to 240 weeks.</P> <P><B>Methods</B></P> <P>One trial enrolled patients with ETV resistance without ADV resistance (n = 90), and another trial included patients with ADV resistance (n = 102). Most patients (91.2%) also had lamivudine resistance. Patients were randomized 1:1 to receive TDF monotherapy or TDF + ETV combination therapy for 48 weeks, and then TDF monotherapy until week 240. We compared efficacy between the studies and safety in the pooled population at 240 weeks.</P> <P><B>Results</B></P> <P>At week 240, the proportion of patients with serum HBV DNA <15 IU/ml was not significantly different between the ETV and ADV resistance groups in the full analysis set (84.4% <I>vs.</I> 73.5%; <I>p =</I> 0.07), which was significantly different by on-treatment analysis (92.7% <I>vs.</I> 79.8%; <I>p =</I> 0.02). Virologic blips associated with poor medication adherence occurred in 7 patients throughout the 240 weeks. None developed additional HBV resistance mutations. Among the 170 HBV e antigen (HBeAg)-positive patients at baseline, 12 (7.1%) achieved HBeAg seroconversion at week 240. None achieved HBV surface antigen seroclearance. Significant decreases from baseline were observed at week 240 in the estimated glomerular filtration rate (−3.21 ml/min/1.73 m<SUP>2</SUP> by the CKD-EPI equation, <I>p <</I>0.001) and bone mineral density (g/cm<SUP>2</SUP>) at the femur (−2.48%, <I>p <</I>0.001).</P> <P><B>Conclusions</B></P> <P>Up to 240 weeks of TDF monotherapy provided an increasing virologic response rate in heavily pretreated patients with HBV resistant to ETV and/or ADV. However, it was associated with poor serological responses and decreasing renal function and bone mineral density.</P> <P>(ClinicalTrials.gov No, NCT01639066 and NCT01639092).</P> <P><B>Lay summary</B></P> <P>In patients chronically infected with hepatitis B virus resistant to multiple drugs including lamivudine, entecavir, and/or adefovir, tenofovir disoproxil fumarate (TDF) monotherapy showed non-inferior efficacy compared with the combination therapy of TDF plus entecavir. Nonetheless, short-term TDF monotherapy was associated with suboptimal virologic response, and its long-term safety was uncertain. This study displayed that 240 weeks of TDF monotherapy provided a virologic response in most of those patients, but it was associated with poor serological responses and decreasing renal function and bone mineral density.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 240 weeks of TDF monotherapy provided an increasing virologic response rate in patients with multidrug-resistant HBV. </LI> <LI> Virologic breakthrough was rare and not associated with emergence of additional resistance mutations. </LI> <LI> The HBeAg seroconversion rate was very low and no patient achieved HBsAg seroclearance up to week 240. </LI> <LI> Prolonged continuous treatment may be needed to maintain viral suppression in these patients. </LI> <LI> Progressive and significant decreases in renal function and bone mineral density after week 144 raise safety concerns. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
( Geum-youn Gwak ),( Young-suk Lim ),( Jonggi Choi ),( Kwan Soo Byun ),( Yoon Jun Kim ),( Byung Chul Yoo ),( So Young Kwon ),( Han Chu Lee ),( Yung Sang Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: To demonstrate whether tenofovir alafenamide (TAF) is efficacious in patients with hepatitis B virus (HBV) resistant to multiple drugs Methods: This was a randomized trial to assess whether switching tenofovir disoproxil fumarate (TDF) to TAF shows non-inferior efficacy and better safety profile in patients with multidrug-resistant HBV compared to continuing TDF. Patients with HBV resistant to entecavir and/or adefovir under TDF monotherapy for at least 96 weeks were randomized 1:1 to switch to TAF or continue TDF for 48 weeks. The primary efficacy endpoint was the proportion of patients with HBV DNA <60 IU/mL in the full analysis set. Results: Of 174 eligible patients under TDF monotherapy, 87 switched to TAF and 87 continued TDF. At baseline, 163 (93.7%) patients had HBV DNA less than 60 IU/mL (96.6% in TAF group vs. 90.8% in TDF group). At week 48, the proportion of patients with HBV DNA <60 IU/mL was 98.9% in TAF group, which was non-inferior to TDF group (97.8%; P=0.99). The proportion of patients with normal ALT (<=40 IU/L) at week 48 tended to be higher in TAF group compared with TDF group (92.0% vs. 79.3%; P=0.06). TAF group showed a significantly higher increase in bone mineral density (BMD) at spine compared with TDF group at week 48 (mean% change, +1.84% vs. 0.08%; P=0.01). TAF group, compared to TDF group, tended to show a larger increase in estimated glomerular filtration rate from baseline as measured by Cockcroft-Gault formula (mean % change, +8.2% vs. +4.5%; P=0.06). Conclusions: In CHB patients with multidrug-resistant HBV, switching TDF to TAF was as effective as TDF in virologic response with improved bone and renal safety.
( Jihyun An ),( Young-suk Lim ),( Geum-youn Gwak ),( Kwan Soo Byun ),( Yoon Jun Kim ),( Byung Chul Yoo ),( So Young Kwon ),( Jonggi Choi ),( Han Chu Lee ),( Yung Sang Lee ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks displayed non-inferior efficacy to TDF plus entecavir (ETV) combination therapy in patients who harbor adefovir (ADV)-resistant hepatitis B virus (HBV). However, whether prolonged TDF monotherapy would be safe and increase the virologic response rate in these patients is unclear. Methods: Among 102 patients with HBV resistant to ADV who were randomized to receive TDF monotherapy (n=50) or TDF/ETV combination therapy (n=52) for 48 weeks, 100 agreed to continue the study on TDF monotherapy, and 96 (94.1%) completed 144 weeks. Results: At baseline, all patients had ADV-resistant HBV mutations; rtA181V/T and/or rtN236T. Most patients (83.3%) also had various combinations of resistance mutations to lamivudine and ETV (rtM204V/I, rtL180M, rtT184A/C/F/G/I/L/S, rtS202G, and rtM250L/V). By intention-to-treat analysis, 62.0% in the TDF-TDF group and 63.5% in the TDF/ETV-TDF group had serum HBV DNA <15 IU/mL at week 48 (P=0.88). At week 144, the proportion increased to 72.0% and 63.5%, respectively (P=0.36). By on-treatment analysis, 81.6% and 89.4%, respectively, had HBV DNA < 60 IU/mL at week 144 (P=0.28). Virologic breakthrough occurred in 2 patients in TDF-TDF group and 2 patients in TDF/ETV-TDF group due to poor drug adherence. At week 144, 12 patients who had HBV DNA >60 IU/mL qualified for HBV genotypic resistance tests, and 4 patients retained some of their baseline resistance mutations. No patients developed additional resistance mutations throughout the study period. Treatment was generally well tolerated. Estimated GFR significantly increased at week 144 from baseline (4.07 mL/min/1.73 m2, P=0.002). The mean change in bone mineral density from baseline at week 144 was 0.33% at spine (P=0.56) and -0.78% at femur (P=0.04). Conclusions: TDF monotherapy was safe and efficacious in patients with ADV-resistant HBV for up to 144 weeks.