Ideal Strategy for the Management of CHB in Asia : Is It Better to Treat Chronic Hepatitis B as Early as Possible?

( Hie Won L. Hann ) 대한간학회 2004 Clinical and Molecular Hepatology(대한간학회지) Vol.10 No.1(S)

48-Week Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) from Tenofovir Disoproxil Fumarate (TDF) in Asian Patients with TDF Risk Factors (RF)

( Won Young Tak ),( Sang Hoon Ahn ),( Seung Woon Paik ),( Jia-Horng Kao ),( Hie-won Hann ),( Fung Scott ),( Trinh Huy ),( Nguyen Tuan Trong ),( Gaggar Anuj ),( Flaherty John ),( Yee Leland J ),( Jump 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: In a recent Phase 3 study (Study 4018) in HBV patients suppressed on TDF treatment, switching to TAF demonstrated noninferior efficacy to continued TDF with superior bone and renal safety at Week 48. This study aims assess the safety and efficacy of switching to TAF from TDF in patients of Asian descent with risk factors for TDF toxicity as per current EASL and AASLD guidelines. Methods: Virally suppressed patients (HBV DNA <20 IU/mL at screening) on TDF were randomized (1:1) to switch to TAF or continue TDF for 48 weeks in a double-blind fashion. Viral suppression and changes in bone (BMD by DXA) and renal (creatinine clearance [eGFR_CG]) parameters were assessed over 48 weeks. Results: Among the 400 Asian patients enrolled, 288 (72%) had at least 1 TDF RF. At Week 48, similar proportions with ≥1 RF had HBV-DNA <20IU/mL (TAF 97%; TDF 97%) and normal ALT by 2018 AASLD criteria (TAF 76%; TDF 73%). TAF subjects with ≥1 RF had increases in eGFR_CG compared to decreases on TDF [median (Q1, Q3) change; TAF: +2.6 (-2.01, 7.34); TDF: -2.7 (-7.56, +15.79); P<0.0001)]. Among patients with ≥1 RF, improvements were seen in BMD for TAF vs. continued declines in TDF patients at both spine (P<0.0001) and hip (P<0.0001). Conclusions: Virally suppressed Asian patients with CHB and risk factors for TDF who switched to TAF showed improved bone and renal safety while efficacy was well-maintained.

Efficacy and Safety of Tenofovir DF (TDF) in Chronic Hepatitis B Patients (CHB) with Lamivudine Resistance (LAM-R): 5-year Results

( Florence Wong ),( Scott Fung ),( Hie-won Hann ),( Magdy Elkhashab ),( Thomas Berg ),( Milotka J. Fabri ),( Andrzej Horban ),( Mijomir Pelemis ),( Ioan Sporea ),( John F. Flaherty ),( Benedetta Masse 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: In CHB patients with LAM-R, TDF has shown efficacy comparableto FTC/TDF and no detectable TDF resistance at 2 years. The final5 year efficacy and safety results from this trial are presented.Methods: CHB patients on LAM with HBV DNA >3 log10 IU/mL andwith documented LAM-R were randomized (1:1) to TDF or FTC/TDFand followed for 5 years.Results: Two hundred eighty patients were randomized; 232 (83%)completed 5 years of treatment. At baseline, mean age was 47 years,most were male (75%) and non-Asian (66%); 53% were HBeAgnegative. Mean HBV DNA was 5.7 log10 IU/mL and 42% had ALT≤ULN at baseline. At Year 5, virologic, serologic, and biochemicalresponses were similar among groups, and remained stable. Ninepatients (4-TDF, 5-FTC/TDF) discontinued due to an adverse event,including increased serum creatinine in 1 patient. For both groupscombined, confirmed renal safety endpoints over 5 years were: CrCL<50 mL/min in 19 (6.8%) patients (12 requiring dose modification),increases in serum creatinine of ≥0.3 and ≥0.5 mg/dL from baselinein 21 (7.5%) and 2 (0.7%) patients, respectively, and serum phosphorus<2 mg/dL in 3 (1.1%) patients. Mean declines in BMD (g/cm2)from baseline for hip and spine BMD, respectively, were 1.7% and1.5% at Year 2, and 2.5%, and 1% at Year 5. Seven patientsexperienced fracture (all except 1 were trauma-related). No TDF resistancewas detected through 5 years by population sequencing.Conclusions: In LAM R patients with CHB treated for 5 years withTDF, a high rate of HBV DNA suppression was achieved and maintainedwith no detectable TDF resistance. There is no apparent ad advantageof combination FTC/TDF in this population. Renal eventsassociated with TDF occurred in up to 7.5% of patients, and averagelosses in bone mineral density of 1 2.5% were observed.

Correlates of Hepatitis B Virus Health‐Related Behaviors of Korean Americans: A Situation‐Specific Nursing Theory

Lee, Haeok,Fawcett, Jacqueline,Yang, Jin Hyang,Hann, Hie‐,Won Blackwell Publishing Inc 2012 JOURNAL OF NURSING SCHOLARSHIP Vol.44 No.4

<P><B>Abstract</B></P><P><B>Purpose</B>: The purpose of this article is to explain the evolution of a situation‐specific theory developed to enhance understanding of health‐related behaviors of Korean Americans (KAs) who have or are at risk for a chronic hepatitis B virus (HBV) infection.</P><P><B>Organizing Construct</B>: The situation‐specific theory evolved from an integration of the Network Episode Model, studies of health‐related behaviors of people with HBV infection, and our studies of and practice experiences with Asian American individuals with HBV infection.</P><P><B>Findings</B>: The major concepts of the theory are sociocultural context, social network, individual‐level factors, illness experience, and health‐related behaviors.</P><P><B>Conclusions:</B> The major propositions of the theory are that sociocultural context, social network, and individual‐level factors influence the illness experience, and that sociocultural context, social network, individual‐level factors, and the illness experience influence health‐related behaviors of KAs who have or are at risk for HBV infection.</P><P><B>Clinical Relevance:</B> This situation‐specific theory represents a translation of abstract concepts into clinical reality. The theory is an explanation of correlates of health‐related HBV behaviors of KAs. The next step is to develop and test the effectiveness of a nursing intervention designed to promote behaviors that will enhance the health of KAs who have or are at risk for HBV infection, and that takes into account sociocultural context, social network, individual‐level factors, and illness experience.</P>

B型肝炎 바이러스가 絲毬體腎炎에 미치는 疫學的 病因論的 硏究

朴漢喆,姜鍾鳴,金箕洪,London,Thomas W.,Hann,Hie Won L.,Blumberg,Baruch S. 한양대학교 의과대학 1982 한양의대 학술지 Vol.2 No.1

HBV와 관계된 抗原,抗體의 複合體가 絲毬體腎炎을 일으키는데 있어 그 寄與度를 알아보기 위하여 소白尿를 동반한 腎疾患患者 116名과 肝疾患을 가진 患者 115名, 그외의 여러疾患患者 127名, 그리고 對照群으로서 建康한 女子 60名과 男子 17名에 대하여 HBsAg, antiHBs 및 antiHBc를 검사하고, 臨床所見을 종합하여 相互의 連關性을 比較하였다. 腎疾患에 있어서 23例에서 腎生檢을 施行하였다. 1. 建康人에 있어서 HBsAg는 7.8%의 陽性率을 보였고, antiHBs는 67.5%, antiHBc는 77.9%에서 陽性이었다. 2. 對象者 全部에 對하여 年齡的으로 볼때, HBsAg의 陽性率은 年齡이 增加함에 따라 차차 減小하지만 antiHBs와 antiHBc는 年齡이 많을수록 增加하여 40歲 以上이면 antiHBs는 70%이상, antiHBc는 90% 이상에서 陽性이 되었다. 3. 腎疾患患者군에 있어서 HBV의 標識, 즉 HBsAg,antiHBs,antiHBc의 陽性率은 建康人群이나 基他疾患群과 다름이 없었고, 肝疾患群에 있어서는 다른 어떤 群보다도 HBsAG와 antiHBc의 陽性이 현저히많았다. 4. 腎生檢한 患者中에서 微少變化性 腎症候群을 除外하고 絲毬體腎炎으로 確定된 12名中 3例, 즉 25%에 있어 HBsAG가 陽性이었고, 이는 對照群 7.8%보다 많으나 統計的으로 意味를 갖기 위하여는 더 많은 標本例가 必要하다. 要컨데 HBV感染으로 絲毬體腎炎이 誘發되는 頻度는 成人에서는 많지 않고, 小兒에서는 좀 더 많을 듯하나 이는 좀더 調査해 보아야 알수 있겠다. 5. 慢性腎不全이 있는 患者群에서 이것이 없는 患者群보다 antiHBs의 陽性率이 높고 感染받지 않은 例가 적었다. 이것은 慢性腎不全患者들이 病院에 出入하면서 HBV에 露出되었고 免疫力도 低下되었기 때문으로 풀이된다. 6. 附隨的으로 HBsAg(+)群에 있어서 尿의 比重이 낮았다. 仔細한 理由는 모르겠으나 HBV가 腎細尿管의 機能에 變化를 준 것이 아닌가 추측된다. A number of reports are now present in which glomerulonephritis is associated with hepatitis B virus(HBV) infection. In persons who carry HBV, HBV antigens and antibodies wax and wane in the blood and form antigen-antibody complex, detectable in the cryoprecipitate or polyethylene glycol precipetate. The antigens and/or antibodies were detectable in the glomerular basement membrane by immunofluorescent studies and were extractable from the basement membrane. It is therefore increasingly evident that HBV infection can cause immune complex mediated glomerulon ephritis. HBV infection is now prevalent in Korea with 7 to 8% positive rate of HBsAg in healthy adults. The purpose of this study is to show the role of HBV antigens in the formation of glomerulonephritis. Patients with significant proteinuria and/or increased levels of SGPT were randon selected and from clinical assessment and biopsies the patients were divided into four groups: 116 cases of patients with glomerulopathy, 115 cases of patients with hepatic diseases, 127 cases with other diseases, and 77 healthy normal control. Sera were separated, stored in -20 degree C. and sent frozen in dry-ice to the Institute for Cancer Reserch, Philadelphia, U.S.A. and were measured for HBsAg, ant i-HBs, and anti-HBc. Results: 1) In healthy normal control group, the HBsAg was positove in 12% of males, 6.7% of females, and 7.8% of both sexes. Anti-HBs was positove in 65% of the male and 68% of the female group. Anti-HBc was positove in 76% of the male and 78% of the female group. 2) As a whole study group, HBsAg positive rate tended to decline as age increased. The positive rates of anti-HBs and anti-HBc were conversely increased. 3) The positive rates of the three HBV markers were statistically not significant between the renal and healthy groups, of between the renal and other disease group. 4) Renal biopsies were performed in 24patients with glomerulonephritis, 3 cases athies were excluded from the study. Of 12 patients with glomerulonephritis, 3cases or 25% were positive for HBsAg. More statistically significant differenences might have been obtained if there were more biopsy samples or if pediatric ages were included 5) Of renal disease group, positive rate of antiHBs was significantly higher in patients with chronic renal failure than those without (77.8% vs 48.5%). Uninfected rate was lower in patients with renal failure than those without (4.4% vs 39.4%). 6) Urinary specific gravity was significantly lower in HBsAg positive group (1.015) than the unifected group (1.020, p less than 0.005). It is specluated that HBV alter the renal concentrating function.

Improvement in Renal Parameters in CHB Patients Treated with Tenofovir Alfenamide (TAF) versus Tenofovir Disoproxil Fumarate (TDF) over 96 Weeks

( Hyung Joon Kim ),( Wan Long Chuang ),( Kosh Agarwal ),( Jae Seok Hwang ),( Florin Caruntu ),( Florence Wong ),( Hie Won Hann ),( John Flaherty ),( Audrey Lau ),( Anuj Gaggar ),( Vithika Suri ),( Shu 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: In Phase 3 studies in CHB patients the efficacy of TAF was found smaller changes in renal parameters compared with TDF treatment. This benefit was particularly evident in patients with risk factors for renal impairment.Here, we present renal safety results after 96 weeks of treatment. Methods: In Phase 3 studies (HBeAg positive patients [N=873] and HBeAg negative patients [N=425]), patients were randomized 2:1 to TAF 25 mg QD or TDF 300 mg QD, and treated for 144 weeks. Renal parameters including estimated glomerular filtration rate (eGFR) calculated by the Cockcroft-Gault method were evaluated. Chronic kidney disease (CKD) staging was categorized by the National Kidney Foundation KDOQI guidelines. Evaluated risk factors for kidney disease included older age (age ≥ 50), female gender, renal impairment (eGFR <90mL/min) and presence of comorbidities (hypertension, cardiovascular disease and diabetes). Urine markers of renal glomerular dysfunction (urine protein and albumin to creatinine ratio) and tubular dysfunction (retinol binding protein (RBP) and beta-2 microglobulin [B2M] to creatinine ratio) were serially assessed. Results: Patients treated with TAF continued to show smaller changes in serum creatinine (p=0.001) and eGFRCG (p<0.001) at 96 weeks. Similarly, median percentage changes in renal tubular markers, were also smaller in TAF-treated patients compared with TDF patients at Week 96; RBP/Cr (p<0.0001) and B2M/Cr (p<0.0001). A lower percentage of patients experienced ≥1 stage worsening in NKF CKD stage when treated with TAF compared with TDF at Week 96 overall and when evaluated by risk factors for kidney disease.Furthermore, CKD stage progression increased disproportionately in the TDF group in patients with ≥2 risk factors (Table). Conclusions: Treatment with TAF for 96 weeks continued to be associated with smaller changes in renal parameters compared with TDF treatment. The benefits of TAF are particularly evident in patients with risk factors for kidney disease.