Incidence, Predictors and Clinical Course of Partial Virologic Response to Tenofovir in Treatment-naive Patients with Chronic Hepatitis B

( Sojung Han ),( Hye Won Lee ),( Beom Kyung Kim ),( Seung Up Kim ),( Jun Yong Park ),( Sang Hoon Ahn ),( Kwang-hyub Han ),( Do Young Kim ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Partial virological response(PVR) to nucleos(t)ide analogues are defined by patients with detectable HBV DNA by real-time PCR assay(> 10-15 IU/ml) at week 48. Clinical importance of NUC PVR relates to the high risk of developing resistance to long-term HBV treatment and requires rescue therapy from potent drugs with high genetic barrier such as entecavir or tenofovir. Long -term ETV therapy is known to result in VR in treatment-naive patients. However, clinical significance of tenofovir is not known. We aim to assess the rates of PVR to tenofovir, the predictive factors associated with PVR, and clinical course in treatment-naive patients with chronic hepatitis B. Methods: Between November 2012 and December 2014, total of 519 treatment naive patients with CHB received first-line tenofovir at Severance Hospital. The primary endpoint was the proportion of patients showing a partial virological response (PVR) during treatment. Multivariate analysis was done to evaluate predictive factors independently associated with the time to PVR. Patients with decompensated liver cirrhosis or HCC or organ transplantation prior to the TDF treatment were excluded. Results: Among 519 patients with tenofovir therapy, virological response was achieved in 400 patients(77%) at 24 weeks of TDF therapy. Upon 48weeks of therapy, 119(22.9%) patients achieved PVR and 45(37.8%) patients achieved VR among PVR patients, following 96weeks of therapy. HBeAg positive patients achieved more PVR(119, 43.59%) compared with HBeAg negative patients(60, 26.4%). Patients with PVR were younger (mean±SD, 47±13 years, P=0.004), had higher baseline HBV DNA levels (6.2±2.1 log10 IU/ml, P=0.009) and showed less HBeAg positivity(54.6%, P<0.001) and less HBeAg seroconversion(32.5%, P<0.001) compared with patients without. Using multivariate analysis, platelet (Odds ratio [OR] 1.005, 95% CI 1.001-1.008, P=0.01) and baseline HBV DNA level (OR 1.172, 95% CI 1.028-1.337, P=0.018) were predictive factors for PVR. Conclusions: Following 24weeks of TDF therapy, 400 patients(77%) achieved VR. 119(22.9%) patients showed PVR after 48weeks of TDF therapy. 96 weeks of TDF therapy results in VR of PVR patients(45, 37.8%) Baseline HBV-PCR(log IU/ml) was higher in patients with PVR than patient without PVR and more patients with HBeAg showed PVR. Patients with PVR achieved less HBeAg seroconversion than patients without PVR. Elevated baseline platelet levels and baseline HBV DNA levels are predictive factors for PVR.

Optimal sequence of systemic therapy after sorafenib failure in patients with hepatocellular carcinoma

Sojung Han,Do Young Kim 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.3

Clinical Outcomes of Hepatic Veno-Occlusive Disease( VOD)/Sinusoidal Obstruction Syndrome(SOS) after Hematopoietic Stem Cell Transplant(HSCT): Single Center Study

( Sojung Han ),( Ahsan Chaudhry ),( Samuel Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Hepatic veno-occlusive disease(VOD), also called sinusoidal obstruction syndrome(SOS), is a potentially life threatening complication primarily associated with hematopoietic cell transplantation( HSCT). VOD/SOS presents with hyperbilirubinemia, ascites, weight gain and painful hepatosplenomegaly. VOD/ SOS with multiorgan failure(MOF) is associated with a high mortality rate (>80%). Defibrotide(25mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States. Methods: Patients who were diagnosed with VOD post HSCT between 2007~2018 were retrospectively reviewed. Patients were diagnosed by Baltimore or modified Seattle criteria or biopsy. Patients received defibrotide or supportive treatment for treatment of VOD. Results: The total number of transplants between 2007~2018 was 800 and 30 patients were diagnosed with VOD. The incidence of VOD was 4%. 7(30.4%) patients were diagnosed within 21 days post HSCT(early onset VOD), and 23(76.7%) patients were diagnosed after 21 days post HSCT(late onset VOD). Post HSCT 100 day survival rates were 70% among VOD patients(n=30), 85.7% among early onset VOD patients(n=7), and 65.2% among late onset VOD patients(n=23). 8(26.7%) patients developed severe VOD and it occurred late onset after 21days post HSCT. 7 patients among severe VOD patients(n=8) received Defibrotide treatment. Survival at day +100 post-HSCT were 75% for patients with severe VOD and 83.4% for severe VOD patients treated with Defibrotide. Survival at day +100 post-HSCT for VOD patients treated with defibrotide(n=13) and patients treated with supportive care(n=17) were 53.8% and 82.4% respectively. 4(30.7%) patients out of 13 patients who received Defibrotide treatment developed bleeding complications. Conclusions: The incidence of VOD was 4% and severe VOD developed at late onset(> Post HSCT 21 days). 26.7% of VOD patients developed severe VOD. Defibrotide treatment did not increase day +100 post-HSCT survival rates.

Sorafenib for 9,923 Patients with Hepatocellular Carcinoma: An Analysis from National Health Insurance Claim Data in South Korea

Han Sojung,Kim Do Young,Lim Ho Yeong,Yoon Jung-Hwan,Ryoo Baek-Yeol,Kim Yujeong,Kim Kookhee,Kim Bo Yeon,Yi So Young,Kim Dong-Sook,Cho Do-Yeon,Yu Jina,Kim Suhyun,Park Joong-Won 거트앤리버 소화기연관학회협의회 2024 Gut and Liver Vol.18 No.1

Background/Aims: Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea. Methods: This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study. Results: Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib; 2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400–600 mg (9.6 months). Conclusions: Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.

YAP/TAZ Expression in Hepatocellular Carcinoma (HCC) and Effects of YAP/TAZ Inhibition on HCC

( Sojung Han ),( Do Young Kim ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Sorafenib for 9,923 Patients with Hepatocellular Carcinoma: An Analysis from National Health Insurance Claim Data in South Korea

( Sojung Han ),( Do Young Kim ),( Ho Yeong Lim ),( Jung Hwan Yoon ),( Baek-yeol Ryoo ),( Yujeong Kim ),( Kook-hee Kim ),( Boyeon Kim ),( So Young Yi ),( Dong-sook Kim ),( Doyeon Cho ),( Jina Yu ),( Su 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: The purpose of this study was to investigate the characteristics, treatment patterns including subsequent treatment and outcomes of sorafenib of whole HCC patients in South Korea. Methods: This is a retrospective, single-arm, and observational study. Data sources came from the national health insurance data. Included patients were those who had been diagnosed as HCC and received sorafenib between 1 July 2008 and 31 December 2014. A total of 9,923 patients were recruited in this study. Results: The mean age of 9,923 patients were 59 years with male predominance (84.6%). The mean HCC-prevalent duration was 663 days (22.1 months). The most common etiology of HCC was hepatitis B (66%). Before sorafenib treatment, 6,669 (67.2%) patients received other kinds of therapies for HCC including transarterial chemoembolization (TACE), resection and radiation therapy. During sorafenib therapy, 1,565 (15.8%) received combined treatment with other modalities. After sorafenib therapy, 2,591 (26.1%) patients received rescue therapies, of which TACE was the most common modality applied in 1,498 (15.1%) patients. The mean duration of sorafenib administration in all the patients was 105.7 days. In 7,159 (72.2%) patients, the initial and mean sorafenib dose were the same. There were 7,023 (70.8%) patients whose initial sorafenib dose was 600-800mg. The survival was longest in patients with recommended starting dose of 800mg, followed by dose reduction to 400mg (15.0 months). The second longest survival was demonstrated in patients with starting dose of 800mg, followed by dose reduction to 400-600mg (9.6 months). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median OS was 14.5 months which were longer than 4.6 months in 7,332 patients who received supportive care after sorafenib. The most commonly applied treatment after sorafenib was TACE (30.8%). Conclusions: Real-life data show that the efficacy of sorafenib seems to be similar with that in clinical trials. Appropriate subsequent therapy after sorafenib might prolong the patient survival.

Comparison of Survival Outcomes According to Additional Therapies (Hepatic Arterial Infusional Chemotherapy versus Sorafenib) after Localized Concurrent Chemoradiotherapy for Advanced HCC

( Sojung Han ),( Beom Kyung Kim ),( Hye Won Lee ),( Jun Yong Park ),( Seung Up Kim ),( Do Young Kim ),( Sang Hoon Ahn ),( Jin-sil Seong ),( Kwang-hyub Han ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Patients with advanced hepatocellular carcinoma (HCC) have a particularly poor prognosis. Even though sorafenib has been approved for treating advanced stage HCC, the unsatisfactory objective response rate still remain unresolved. Localized concurrent chemoradiotherapy (CCRT) has shown the significant activity for advanced stage HCC, through initial tumor reduction. In the current study, we aimed to compare survival outcomes according to the additional sequential modalities (hepatic arterial infusional chemotherapy [HAIC] vs. sorafenib) after localized CCRT for advanced HCC. Methods: We analyzed a total of 343 patients who were treated with localized CCRT for advanced HCC. In the course of radiotherapy for 5 weeks, hepatic arterial infusion of 5-fluorouracil (500mg/day) via implanted port was applied during the first 5 and the last 5 days of radiotherapy. Four weeks after localized CCRT, 296 patients received HAIC with 5- fluorouracil and cisplatin every 4 weeks (CCRT-HAIC group), whereas 47 received sorafenib treatment (CCRT-SOR group). The primary endpoint was overall survival (OS). Results: Among the entire population, the mean age was 58.6 years old (293 male). One hundred sixty four patients had major portal vein invasion (tumor invasion at main trunk or the first order branch). All had well-preserved liver function (Child-Pugh class A). The median OS was 18.0 months. Between CCRT-HAIC and CCRT-SOR group, there was no significant difference in the mean age (p=0.437) and the proportion of male gender (p=0.41) and major portal vein invasion (p=0.868). There was no significant difference in the median OS between two groups (18.0 vs. 18.4 months, respectively; p=0.892). Among a subgroup with major portal vein invasion, there was no significant difference in the median OS between two groups (14.0 vs. 13.0 months, respectively; p=0.892) Conclusions: Survival outcomes according to additional sequential modalities after CCRT (HAIC vs. sorafenib) were similar for advanced HCC. Further randomized trial should be required to make the more robust evidence.

Clinical Outcomes for Advanced HCCs: A Chronological Comparison from a Single Center Experience

( Sojung Han ),( Beom Kyung Kim ),( Hye Won Lee ),( Jun Yong Park ),( Seung Up Kim ),( Do Young Kim ),( Sang Hoon Ahn ),( Jin-sil Seong ),( Kwang-hyub Han ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Patients with advanced stage of hepatocellular carcinoma (HCC) have poor prognosis. In the current study, we aimed to conduct a chronological comparison about survival outcomes for those with advanced stage HCC from 2003 to 2016. Methods: We retrospectively analyzed 939 patients with advanced HCCs treated with localized concurrent chemoradiotherapy (CCRT) or hepatic arterial infusional chemotherapy (HAIC) as the first-line treatment from 2003 to 2016 at Severance Hospital. Four hundred eighty seven patients were treated from 2003 to 2008 (group A), whereas 452 patients were treated from 2009 to 2016 (group B). Patients with Child-Pugh class A or B were included. Overall survival (OS) was assessed. Results: The mean age of the whole population was 56.2 years old and 800 patients(85.2%) were male. The median overall survival(OS) was 10.0months. Patients in group B were older than those in group A(58.1 vs. 54.5, respectively, p=0.001) There was no difference in gender between two groups (p=0.408). Group B had the longer median OS compared to group A (15.0 vs. 7.4 months, respectively, p=0.001). Among those treated with localized CCRT, group B had the longer median OS than group A (17.0 vs. 11.3 months, respectively, p=0.001). Likewise, among patients treated with HAIC, group B had the longer median OS than group A (7.0 vs. 5.4 months, respectively, p=0.001). Conclusions: Survival outcomes of those with advanced stage HCC improved over time. Further validation studies are required to confirm such a clinical trend.

Long-Term Outcomes of Liver-Directed Concurrent Chemoradiotherapy for Hepatocellular Carcinoma with Major Portal Vein Invasion

( Sojung Han ),( Hye Won Lee ),( Jun Yong Park ),( Seung Up Kim ),( Do Young Kim ),( Sang Hoon Ahn ),( Kwang-hyub Han ),( Jinsil Seong ),( Jong Yun Won ),( Beom Kyung Kim ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: We aimed to assess therapeutic efficacy of liver-directed concurrent chemoradiotherapy (LD-CCRT) in HCC patients with major portal vein (PV) invasion Methods: HCC patients with PV invasion (main trunk or the 1^st order branch) between 2008 and 2016 were enrolled. During a 5-week radiotherapy course, concurrent hepatic arterial infusion with 5-fluorouracil (5FU) and leucovorin were administered through an implanted port on the first and last 5 days. Four weeks after LD-CCRT, hepatic arterial infusion chemotherapy (HAIC) using 5FU and cisplatin were administered for maintenance. The endpoints were overall survival (OS), progression-free survival (PFS), and response rates. Results: 152 patients were enrolled, and objective response rate was 48.0% at 4 weeks after LD-CCRT which has increased up to 55.3% during HAIC maintenance. After LD-CCRT, biological responses in alpha-fetoprotein (AFP) and protein induced by the absence of vitamin K or antagonist-II levels (PIVKA-II) were achieved in 46.2% and 52.6% of patients, respectively. Sixteen patients (10.5%) underwent curative resection or liver transplantation after down-staging. Median OS and PFS were 14.0 and 7.0 months, respectively. Conclusions: LD-CCRT followed by maintenance HAIC yielded favorable OS and PFS in advanced HCC patients with major PV invasion. Tumor reduction by initial LD-CCRT enabled down-staging, subsequent curative treatment, and long-term survival in 10.5% of patients. Further prospective trials are required to confirm these results.

S-4 Incidence, predictors and clinical course of PVR to tenofovir in NUC-naive patients with CHB

( Sojung Han ),( Hye Won Lee ),( Beom Kyung Kim ),( Seung Up Kim ),( Jun Yong Park ),( Sang Hoon Ahn ),( Kwang Hyub Han ),( Do Young Kim ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1

Background: Partial virological response (PVR) to nucleos(t)ide analogues (NUC) are defined by patients with detectable HBV DNA (>10-15 IU/ml) at week 24 or week 48. Clinical importance of NUC PVR relates to developing resistance to long-term HBV treatment and requires rescue therapy from potent drugs such as entecavir(ETV) or tenofovir (TDF). Third generation NUCs (ETV, TDF) carry lower risk of resistance to long-term monotherapy, and the association between PVR and secondary treatment failure is not well established. There are studies regarding the efficacy of long?term ETV therapy. However, clinical significance of long term TDF is not known. We aim to assess the prevalence of PVR to TDF, the predictive factors associated with PVR, and clinical course in treatment-naive patients with chronic hepatitis B. Methods: We retrospectively analyzed 566 treatment naive patients with CHB who received TDF monotherapy over 6months at Severance Hospital. PVR at week 24 and week 48 were compared against patients with Complete virologic response (CVR) at 6months. Multivariate analysis was done to evaluate predictive factors of PVR. Cumulative probability of CVR was compared in patients with PVR. Results: Among 566 patients with TDF, 452 (79.9%) patients achieved CVR upon 48 weeks of TDF therapy and 510 (90.1%) achieved CVR after 96 weeks of TDF therapy. 241 (42.5%) of NUC-naive patients treated with TDF achieved PVR at week 24, and 114 (20.1%) patients achieved PVR at week 48. Using multivariate analysis, HBeAg positivity (Odds Ratio [OR] 2.501, 95% CI 1.56-4.010, p<0.0001) and baseline HBV DNA level (OR 1.633, 95% CI 1.386-1.909, p<0.0001) were predictive factors for PVR at week 24. Only baseline HBV DNA level (OR 1.813, 95% CI 1.432-2.295) was predictive factor for PVR at week 48. Cumulative CVR was significantly different (p=0.005) among patients with PVR at week 24 with HBV DNA levels <7 log10 IU/mL and patients with HBV DNA level≥7 log10IU/mL. Conclusions: Elevated baseline HBV-DNA level was both associated with PVR at week 24 and PVR at week 48. HBeAg positivity was associated with PVR at week 24. Prolonged TDF therapy in NUC-naive patients with PVR leads to CVR of majority of patients.