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HBV : Quantitative Hepatitis B Surface Antigen Kinetics in Entecavir Treated Patients
( Ju Yeon Cho ),( Yong Han Paik ),( Seon Woo Kim ),( Sook Young Woo ),( Won Sohn ),( Geum Youn Gwak ),( Moon Seok Choi ),( Joon Hyeok Lee ),( Kwang Cheol Koh ),( Seung Woon Paik ),( Byung Chul Yoo ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Hepatitis B surface antigen (HBsAg) loss is associated with immunological control of the hepatitis B virus and durable suppression of viral replication. HBsAg levels reflect transcription of closed covalent circular DNA in patients with chronic hepatitis B (CHB). The aim of this study was to investigate the on-treatment kinetics of quantitative HBsAg during entecavir therapy to predict the treatment period needed to achieve HBsAg seroconversion. Methods: From a cohort of 1006 CHB treatment-naive patients who were started on entecavir, 426 patients with a quantitative HBsAg value after initiation of entecavir were selected. Among the patients, 321 patients (75.1%) had more than 2 serial samples. The kinetics of quantitative HBsAg decline was assessed using 1469 samples by mixed linear model to predict the time to clear HBsAg while on entecavir treatment. Results: Among the 426 patients, 221 patients (51.9%) were HBeAg positive and 205 patients (48.1%) were HBeAg negative. At baseline, the age of the HBeAg(-) group was significantly older (P<0.001) and the level of HBV-DNA was significantly lower (P<0.001) compared to the HBeAg (+) group. During a median follow up of 49.5 months, the quantitative HBsAg level showed a slow but consistent decrease in value regardless of the HBeAg status. The HBeAg-positive group had a mean slope of -0.0077 ± 0.0011 Log10 IU/month (P<0.001) and the HBeAg-negative group had a mean slope of -0.0052 ± 0.0010 Log10 IU/month (P<0.001). The calculated time to clear quantitative HBsAg in HBeAg-positive and HBeAg-negative groups were 37 years and 50 years, respectively. Conclusions: The analysis of kinetics for HBsAg level during entecavir therapy suggests the treatment period required to achieve quantitative HBsAg clearance during entecavir therapy is life-long, regardless of the HBeAg status of chronic hepatitis B patients.
( Ju Yeon Cho ),( Yong Han Paik ),( Ho Young Lim ),( Yang Won Min ),( Geum Youn Gwak ),( Moon Seok Choi ),( Joon Hyeok Lee ),( Kwang Cheol Koh ),( Seung Woon Paik ),( Byung Chul Yoo ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1
Background: Sorafenib is an orally active multikinase inhibitor that is approved for the treatment of advanced hepatocellular carcinoma (HCC). However, clinical parameters that may predict the treatment outcomes in sorafenib-treated advanced HCC patients remains unknown. Methods: A total of 93 advanced HCC patients who were treated with sorafenib as the initial treatment modality from January 2007 to September 2011 were retrospectively reviewed. Overall survival was the primary endpoint for the analysis. Various clinical parameters including patient demographics, Child-Pugh score, portal vein thrombosis, lymph node metastasis, positron emission tomography (PET) standardized uptake value (SUV) of the most hypermetabolic lesion, and adverse effects to sorafenib were analyzed. Univariate and multivariate analysis was carried out to identify clinical parameters as predictor of the effect of sorafenib. Results: There were 82 males and 11 females included in the study, with a mean age of 54 years. The overall survival was 3.4 months (95% CI: 2.5-4.3). 92 patients were Child-pugh class A or B and 1 Child-pugh class C patient was included. The BCLC staging of the patients was advanced in 92 patients and terminal in 1 patient. Chronic hepatitis B was the predominant cause of HCC (79.5%). Noted adverse effects were hand-foot syndrome, diarrhea, fatigue, abdominal pain, nausea and stomatitis. Univariate analysis showed that the presence of adverse effects such as hand-foot syndrome (n=22) and diarrhea (n=19) were associated with a longer overall survival duration (6.7 months vs 2.5 months, p=0.014 and 6.6 months vs 2.7 months p=0.044, respectively). The presence of hand-food syndrome predicted a better overall survival in the multivariate analysis (p=0.001). Conclusions: Advanced HCC patients treated with sorafenib who experienced hand-foot syndrome and diarrhea showed better overall survival than patients without these side effects. These side effects may be used as clinical parameters for the prediction of sorafenib response in patients with HCC.
( Ju-yeon Cho ),( Moon Seok Choi ),( Gil Sun Lee ),( Won Sohn ),( Jemma Ahn ),( Dong-hyun Sinn ),( Geum-youn Gwak ),( Yong-han Paik ),( Joon Hyeok Lee ),( Kwang Cheol Koh ),( Seung Woon Paik ) 대한간학회 2016 Clinical and Molecular Hepatology(대한간학회지) Vol.22 No.4
Background/Aims: Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA―a dreadful event limiting further curative treatment―have not been fully evaluated. Methods: In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated. Results: During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence. Conclusions: Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence. (Clin Mol Hepatol 2016;22:477-486)
( Ju-yeon Cho ),( Won Sohn ),( Dong-hyun Sinn ),( Geum-youn Gwak ),( Yong-han Paik ),( Moon Seok Choi ),( Kwang Cheol Koh ),( Seung Woon Paik ),( Byung Chul Yoo ),( Joon Hyeok Lee ) 대한내과학회 2017 The Korean Journal of Internal Medicine Vol.32 No.4
Background/Aims: Entecavir is a potent nucleoside analogue with high efficacy and barrier for resistance. We aimed to investigate the long-term efficacy and viral resistance rate of entecavir and explore the factors associated with virologic response, including quantitative hepatitis B surface antigen (qHBsAg) levels. Methods: One thousand and nine treatment-naive chronic hepatitis B (CHB) patients were evaluated for cumulative rates of virologic response, biochemical response, and entecavir mutations. The role of baseline qHBsAg for virologic response was assessed in 271 patients with qHBsAg prior to entecavir treatment. Results: The median duration of entecavir treatment was 26.5 months. The cumulative rate of virologic response at years 1, 3, and 5 were 79.0%, 95.6%, and 99.4%, respectively. The cumulative rate of entecavir resistance was 1.0% and 2.1% in years 3 and 5. Multivariate analysis identified baseline hepatitis B e antigen (HBeAg) negative status (p < 0.001) and lower hepatitis B virus (HBV) DNA (p < 0.001) as predictors of virologic response. Lower qHBsAg was an independent predictor of virologic response in patients with baseline qHBsAg. There were no serious adverse events during treatment. Conclusions: Long-term entecavir treatment of nucleos(t)ide-naive CHB patients was associated with an excellent virologic response and a low rate of entecavir-resistant mutations at 5 years. Baseline HBV DNA load, qHBsAg levels, and HBeAg status were predictors of virologic response during entecavir treatment.
( Hyo Jin Kim ),( Ju Yeon Cho ),( Yu Jin Kim ),( Geum Youn Gwak ),( Yong Han Paik ),( Moon Seok Choi ),( Kwang Cheol Koh ),( Seung Woon Paik ),( Byung Chul Yoo ),( Joon Hyeok Lee ) 대한내과학회 2015 The Korean Journal of Internal Medicine Vol.30 No.1
Background/Aims: The efficacy of tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B (CHB) patients following prior treatment failure with multiple nucleos(t)ide analogues (NAs) is not well defined, especially in Asian populations. In this study we investigated the effi cacy and safety of TDF rescue therapy in CHB patients after multiple NA treatment failure. Methods: The study retrospectively analyzed 52 CHB patients who experienced failure with two or more NAs and who were switched to regimens containing TDF. The effi cacy and safety assessments included hepatitis B virus (HBV) DNA undetectability, hepatitis B envelop antigen (HBeAg) seroclearance, alanine transaminase (ALT) normalization and changes in serum creatinine and phosphorus levels. Results: The mean HBV DNA level at baseline was 5.4 ± 1.76 log10 IU/mL. At a median duration of 34.5 months of TDF treatment, the cumulative probabilities of achieving complete virological response (CVR) were 25.0%, 51.8%, 74.2%, and 96.7% at 6, 12, 24, and 48 months, respectively. HBeAg seroclearance occurred in seven of 48 patients (14.6%). ALT levels were normalized in 27 of 31 patients (87.1%) with elevated ALT at baseline. Lower levels of HBV DNA at baseline were signifi- cantly associated with increased CVR rates (p < 0.001). However, CVR rates did not differ between TDF monotherapy or combination therapy with other NAs, and were not affected by mutations associated with resistance to NAs. No significant adverse events were observed. Conclusions: TDF is an effi cient and safe rescue therapy for CHB patients after treatment failure with multiple NAs.
( Jem Ma Ahn ),( Ju Yeon Cho ),( Won Sohn ),( Geum Youn Gwak ),( Yong Han Paik ),( Moon Seok Choi ),( Joon Hyeok Lee ),( Kwang Cheol Koh ),( Seung Woon Paik ),( Byung Chul Yoo ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: In patients with liver cirrhosis, high prevalence of diabetes has been reported from many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by fibroscan with the diabetes mellitus in patients with chronic liver diseases. Methods: The study population consisted of 567 chronic liver disease patients, all of whom took fibroscan for evaluating the degree of hepatic fibrosis and steatosis. The patients who had high ALT (>2xUNL), total bilirubin (>2 mg/dL), IQR/median (>0.3) were excluded. Diabetes was diagnosed when it was previously diagnosed by doctor or fasting plasma glucose was more than 126 mg/dL or HbA1c was more than 6.5% at least 2 times. Cut-off LSM levels for significant fibrosis (≥F2) and cirrhosis (≥F4) was 8.0 kPa, and 14.0 kPa, respectively. The degree of steatosis was graded by CAP score (mild steatosis (S1): 239- 258 db/m, moderate steatosis (S2): 259-292 db/m, severe steatosis (S3): >292 db/m). 0 셀 (0.0%)은(는) 5보다 작은 기대 빈도를 가지는 셀입니다. 최소 Results: Among 567 patients, 74% were with HBV, 14% with HCV, 7.4% with alcoholic liver disease, and 3.9% with NAFLD. Impaired fasting glucose was observed in 184 of 567 (32%) and diabetes was diagnosed in 84 of 567 (15%). High prevalence of diabetes was observed in alcoholic liver disease (35%), NAFLD (22%), and HCV (17%) compared with HBV (12%) (P<0.001 ). Diabetes was more commonly observed in patients with significant fibrosis (F0/1 (9%), F2/3 (14%), F4 (31%), P<0.001). DM prevalence was higher in patients with moderate to severe steatosis (S0/1 (13%), S2/3 (18%), P<0.001). Regarding life styles, there was significant association of diabetes with older age (>50 years), gender (male), obesity (BMI>25), smoking, hypertension, hyperlipidemia. Conclusions: The patients with chronic liver diseases show high prevalence of diabetes in order of alcoholic liver disease, NAFLD, Hepatitis C, and Hepatitis B. The degree of fibrosis and steatosis assessed by fibroscan has significant relationship with the prevalence of diabetes in patients with chronic liver disease.
( Jung Min Ha ),( Won Sohn ),( Ju Yeon Cho ),( Jeung Hui Pyo ),( Kyu Choi ),( Dong Hyun Sinn ),( Geum-youn Gwak ),( Moon Seok Choi ),( Joon Hyeok Lee ),( Kwang Chul Koh ),( Seung Woon Paik ),( Byung C 대한간학회 2015 Clinical and Molecular Hepatology(대한간학회지) Vol.21 No.3
Background/Aims: Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. Methods: Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. Results: A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (≥28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (≥grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group ( P=0.016). Conclusions: Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-Brelated acute-on-chronic liver failure. (Clin Mol Hepatol 2015;21:232-241)
( Won Sohn ),( Moon Seok Choi ),( Ju Yeon Cho ),( Geum Youn Gwak ),( Yong Han Paik ),( Joon Hyeok Lee ),( Kwang Cheol Koh ),( Seung Woon Paik ),( Byung Chul Yoo ) 대한소화기학회 2014 Gut and Liver Vol.8 No.5
Background/Aims: The role of radiofrequency ablation (RFA) remains uncertain in patients with viable hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). Methods: A total of 101 patients (April 2007 to August 2010) underwent RFA for residual or recurrent HCC after TACE. We analyzed their long-term outcomes and predictive factors. Results: The overall survival rates after RFA were 93.1%, 65.4%, and 61.0% at 1, 3, and 5 years, respectively. Predictive factors for favorable overall survival were Child- Pugh class A (hazard ratio [HR], 3.45; p=0.001), serum α-fetoprotein (AFP) level <20 ng/mL (HR, 2.90; p=0.02), and recurrent tumors after the last TACE (HR, 3.14; p=0.007). The cumulative recurrence-free survival rate after RFA at 6 months was 50.1%. Predictive factors for early recurrence (within 6 months) were serum AFP level ≥20 ng/mL (HR, 3.02; p<0.001), tumor size ≥30 mm at RFA (HR, 2.90; p=0.005), and nonresponse to the last TACE (HR, 2.13; p=0.013). Conclusions: Patients with recurrent or residual HCC who undergo prior TACE show a favorable overall survival, although their tumors seem to recur early and frequently. While good liver function, a low serum AFP level, and recurrent tumors were independent predictive factors for a favorable overall survival, poor response to TACE, a high serum AFP level, and large tumors are associated with early recurrence. (Gut Liver 2014;8:543-551)