Efficacy of Sofosbuvir and Ribavirin Treatment in Genotype 2 HCV Infected Patients: A Real Life and Multicenter Study

( Chang Hwi Yoon ),( Seung Kak Shin ),( Young-joo Jin ),( Jin-woo Lee ),( Oh Sang Kwon ),( Yun Soo Kim ),( Duck Joo Choi ),( Ju Hyun Kim ),( Sangheun Lee ),( Ki Jun Han ),( Young Nam Kim ),( Tae Hun K 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Sofosbuvir (SOF) and weight-based ribavirin (RBV) for 12 or 16 weeks (for liver cirrhosis, LC) is recommended for the treatment of patients with chronic hepatitis C virus (HCV) genotype 2 (GT2) infection. The efficacy in virologic response, improvement of liver function and non-invasive fibrosis marker in LC were investigated. Methods: All HCV GT2 patients who were treated with SOF and RBV for at least 4 weeks from March 2016 to January 2017, were retrospectively enrolled. Virologic response was measured at 4 weeks (rapid virologic response, RVR), at 12 weeks or 16 weeks (end of treatment response, ETR), and at 12 weeks after the end of treatment (sustained virologic response, SVR12). Liver function, aspartate transaminase to platelet ratio index (APRI), FIB-4 index, and fibrosis index (FI) were compared between before and after treatment (SVR12) Results: A total of 150 patients were treated with SOF and RBV for at least 4 weeks. Baseline characteristics were obtained: age (55±12 years), gender (male: 47.3%), LC (22.0%), treatment-naïve (85.3%), ALT (67.5±59.4 IU/L), HCV RNA (2,107,021±3,069,914 IU/mL). RVR (138/146, 94.5%), ETR (118/119, 99.2%), and SVR (62/64, 96.9%) rates were obtained. SVR rates were not significantly different between non-LC (47/47, 100%) and LC patients (15/17, 88.2%) (p=0.067). SVR rates were not significantly different between treatment- naïve (49/50, 98.0%) and treatment-experienced patients (13/14, 92.9%) (p=0.392). In LC patients (n=33), there were significant changes of albumin level (3.7±0.5 to 3.9±0.7 g/dL, p=0.057), platelet count (99.0±41.5 to 120.5±55.8 x103/mm3, p=0.021), APRI (2.9±1.7 to 0.9±0.6, p<0.001), FIB-4 (8.9±5.9 to 4.7±3.1, p<0.001), and FI (3.3±0.8 to 2.9±0.9, p=0.005) after treatment. RBV dose reduction was requested in 13 (10.9%) patients due to anemia. Conclusions: SOF and RBV treatment for HCV GT2 infected Korean subjects achieved high SVR rates. In addition, improvement of liver function and non-invasive fibrosis marker were noted in LC patients

Surgery versus Locoregional Treatment in BCLC Stage 0 HCC Patients

( Jung Mi Chang ),( Soon Ho Um ),( Tae Hyung Kim ),( Han Ah Lee ),( Dae Hoe Gu ),( Jem Ma Ahn ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Yoon Tae Jeen ),( Hong Sik Lee ),( Hoon Jai Chun ),( Chang Duck K 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: The aim of this study is to compare the outcome between surgical treatment and locoregional treatment in very early stage hepatocellular carcinoma(BCLC stage 0) patients retrospectively. Methods: The survival rates of hepatocellular carcinoma patients who were newly diagnosed at Korea University Anam Hospital from March 2004 to December 2015 and whose liver function was Child-Pugh grade A and BCLC 0 (n =203) were compared according the treatment methods. In the surgical group (n=54), all patients underwent partial hepatectomy, and in the locoregional treatment group (n=149), patients who underwent TACE, RFA/PEI, and both TACE and RFA/PEI were included. Kaplan-Meier method, log-rank test and univariate multivariate Cox regression analysis were used for statistical analysis. Results: The median age of all patients was 60 years and male accounted for 70.9%. In the univariate analysis, the median survival time of the surgical group was 4345 days(95% CI 1000~7689) and the median survival time of the non-surgical group was 2923 days (95% CI 2395 ~ 3450).The survival time of the surgical group was longer than that of the non-surgical group, but the difference in survival rates between the two groups was not significant (log-rank P = 0.121). The cumulative survival rates of the surgical group in year 1, 3, 5, 7, 9 were 98%, 88.8%, 75.1%, 69.7%, and 69.7%, respectively, and the rates of the non-surgical group were 96.6%, 82.7%, 73.5%, 57.8% and 44.6%, respectively. On the other hand, age, albumin and MELD score were significantly correlated with patient survival (P<0.005) and the surgical group was younger and had higher albumin level and lower MELD score at baseline (P<0.05). The difference in survival rates between the two groups was not significant when these factors were adjusted in multivariate analysis.(P=0.738, HR 1.130, 95% CI 0.552-2.315) Conclusions: In patients with HCC of the very early stage of BCLC, there was no significant difference in survival rates statistically between the surgical and non-surgical groups.

Comparative Analysis of Physicochemicals and Antioxidative Properties of New Giant Embryo Mutant, YR23517Acp79, in Rice (Oryza sativa L.)

Seo, Woo-Duck,Kim, Jun-Young,Park, Dong-Soo,Han, Sang-Ik,Jang, Ki-Chang,Choi, Kyung-Jin,Kim, Sang-Yeol,Oh, Seong-Hwan,Ra, Ji-Eun,Yi, Gi-Hwan,Park, Soo-Kwon,Hwang, Woon-Ha,Song, You-Chun,Park, Bo-Ram,K The Korean Society for Applied Biological Chemistr 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.5

Nutritional and physicochemical properties of new giant embryo mutant rice (YR23517Acp79, YR) were analyzed. YR exhibited increased total protein (9.3${\pm}$0.3%), lipid (3.7${\pm}$1.1%), amino acid (663.28${\pm}$1.9 mg/g), and mineral contents (Ca=284.0${\pm}$6.2, Mg=1417.5${\pm}$13.6 mg/kg). In YR brown rice four major physicochemicals, including gamma-aminobutyric acid (brown rice= 0.46${\pm}$0.014 mg/g), ${\gamma}$-oryzanol (0.43${\pm}$0.021 mg/g), vitamin $B_1$ (6.42${\pm}$0.3 mg/kg), and tocopherols (alpha= 2.68${\pm}$0.1, beta=0.11${\pm}$0.01, gamma=0.05${\pm}$0.001 mg/100 g) increased in comparison to reported giant embryo (Keunnunbyeo, KB) and normal embryo rice (Ilmibyeo, IB). YR showed higher scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (0.2 g/mL=57.1${\pm}$2.25) and 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (0.2 g/mL=50.2${\pm}$1.45) radicals but also inhibited lipopolysaccharide-induced nitric oxide production without cytotoxicity. These results indicate YR is a high quality functional rice due to its high nutrition content and antioxidant effects of physicochemicals.

The Outcome of Surgical Treatment versus Local Regional Treatment in BCLC Stage a Hepatocellular Carcinoma Patients

( Jung Mi Chang ),( Soon Ho Um ),( Tae Hyung Kim ),( Han Ah Lee ),( Dae Hoe Gu ),( Jem Ma Ahn ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Yoon Tae Jeen ),( Hong Sik Lee ),( Hoon Jai Chun ),( Chang Duck K 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: The aim of this study is to compare the outcome between surgical treatment and local regional treatment in early stage hepatocellular carcinoma(BCLC stage A) patients retrospectively. Methods: The survival rates of hepatocellular carcinoma patients who were newly diagnosed at Korea University Anam Hospital from March 2004 to December 2015 and whose liver function was Child-Pugh grade A and BCLC A (n = 306) were compared according the treatment methods. In the surgical group (n=118), all patients underwent partial hepatectomy, and in the locoregional treatment group (n=188), patients who underwent TACE, RFA/PEI, and both TACE and RFA/PEI were included. Kaplan-Meier method, log-rank test and univariate multivariate Cox regression analysis were used for statistical analysis. Results: The median age of all patients was 60.3 years and male accounted for 76.1%. %. In the univariate analysis, the cumulative survival rates of the surgical group in year 1, 3, 5, 7, 9 were 94.8%, 83.5%, 77.3%, 66.7%, and 60%, respectively, and the rates of the non-surgical group were 93.2%, 76.1%, 57.3%, 48.7%, and 34.8%, respectively. The survival rates of both groups were significantly different. (log-rank P = 0.002). But the difference in survival rates between the two groups was not significant (P = 0.159) when the factors significantly correlated with patient survival (age, albumin, bilirubin, INR and MELD score) were adjusted in multivariate analysis. So subgroup analysis based on size and number of tumors were performed. In a single mass subgroup (n=209), univariate analysis showed a significant difference in the survival rates between the surgical group and the non-surgical group when the tumor size was less than 5cm, but multivariate analysis did not show the difference. However, there was a significant difference in the survival rates between the surgical group and the non-surgical group when the tumor size was bigger than 5cm (n=37), and multivariate analysis did show the difference after adjusting for age, albumin, bilirubin, INR, and MELD score as well.(P=0.001). In the subgroup with multiple (2-3) unilobar mass (≦3cm), there were no difference between the survival rates of the surgical group and non-surgical group and not even after adjustment of previously mentioned factors (p>0.05). Conclusions: In patients with HCC of BCLC stage A, surgery had better survival benefits over non-surgical treatment if the number of tumor was one and the tumor was larger than 5 cm.

Synthesis and electrochemical studies of nano-scale carbon-coated LiFePO4 electrodes for Li-ion batteries.

Jeong, Euh Duck,Kim, Hye Jin,Ahn, Chang Won,Ha, Myoung Gyu,Hong, Tae Eun,Kim, Hyun Gyu,Jin, Jong Sung,Bae, Jong Sung,Hong, K S,Kim, Yang-Soo,Kim, Hae-Jin,Doh, C H,Yang, H S American Scientific Publishers 2009 Journal of nanoscience and nanotechnology Vol.9 No.7

<P>Regardless of high capacity and stability during lithium extraction, LiFePO4 materials have difficulty in the applications for high electrical density because of low electrical conductivities. In order to optimize this problem, we synthesized carbon coated LiFePO4 by adding humic acid using solid state reaction method. We characterized the synthesized compounds via the crystallinity, the valence states of Fe ions, and their shapes. We found the carbon coating using X-ray photoelectron spectroscopy (XPS) and transmission electron microscope (TEM). We also found that the iron ion is substituted from 3+ to 2+ through XPS measurement. We showed that the carbon coating increased the electrochemical behavior by measuring the charge-discharge characteristics.</P>

Efficacy of Daclatasvir and Asunaprevir Treatment in Genotype 1b HCV Infected Patients: A Real Life and Multicenter Study

( Seung Kak Shin ),( Oh Sang Kwon ),( Chang Hwi Yoon ),( Young-joo Jin ),( Jin-woo Lee ),( Sangheun Lee ),( Ki Jun Han ),( Young Nam Kim ),( Tae Hun Kim ),( Yun Soo Kim ),( Duck Joo Choi ),( Ju Hyun K 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Combination of daclatasvir (DCV) and asunaprevir (ASV) has been approved in Korea for the treatment of genotype 1b (GT1b) hepatitis C virus (HCV) infected patients. The efficacy in virologic response, improvement of liver function and non-invasive fibrosis marker in liver cirrhosis (LC) were investigated. Methods: All HCV GT1b patients who were treated with DCV and ASV for at least 4 weeks from August 2015 to January 2017, were retrospectively enrolled. Virologic response was measured at 4 weeks (rapid virologic response, RVR), at 24 weeks (end of treatment response, ETR), and at 12 weeks after the end of treatment (sustained virologic response, SVR12). Liver function, aspartate transaminase to platelet ratio index (APRI), FIB-4 index, and fibrosis index (FI) were compared between before and after treatment (SVR12). Results: Patients with GT1b patients (n=474) were examined for resistance associated variants (RAVs). Sixty-seven patients had RAV. A total of 290 RAV-negative patients were treated with DCV and ASV for at least 4 weeks. Baseline characteristics were obtained: age (54±11 years), gender (male: 50.3%), LC (29.0%), treatment-naïve (74.8%), ALT (58.5±49.2 IU/L), HCV RNA (1,915,001±4,969,456 IU/mL). RVR (255/277, 92.1%), ETR (190/195, 97.4%), and SVR (146/152, 96.1%) rates were obtained. SVR rates were not significantly different between non-LC (102/104, 98.1%) and LC patients (44/48, 91.7%) (p=0.080). SVR rates were not significantly different between treatment- naïve (103/106, 97.2%) and treatment-experienced patients (43/46, 93.5%) (p=0.368). In LC patients (n=48), there were significant changes of albumin (3.8±0.8 to 4.0±0.5 g/dL, p=0.036), platelet count (109.6±52.6 to 120.3±58.5 x103/mm3, p=0.004), APRI (2.6±3.1 to 0.8±0.6, p=0.001), FIB-4 (7.6±6.5 to 2.9±1.6, p<0.001), and FI (3.1±1.1 to 2.9±1.2, p=0.058) after treatment. Conclusions: DCV and ASV treatment for HCV GT1b infected Korean subjects without RAV achieved high SVR rates. In addition, improvement of liver function and non-invasive fibrosis marker were noted in patients with LC.

Treatment and Prognosis of Advanced HCC with Metastasis

( Tae Hyung Kim ),( Soon Ho Um ),( Han Ah Lee ),( Jung Mi Chang ),( Dae Hoe Gu ),( Jem Ma Ahn ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Yoon Tae Jeen ),( Hong Sik Lee ),( Hoon Jai Chun ),( Chang Duck K 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: As hepatocellular carcinoma (HCC) progresses, it is accompanied by deterioration of liver function, which makes treatment difficult. In particular, advanced HCC involves not only impairment in liver function and general condition but also vascular invasion and other organ metastasis. It is very heterogeneous stage and needs to be further subdivided. In the present study, we investigated treatment outcomes and the factors associated with prognosis in HCC patients with distant metastasis. Methods: We analyzed data of 103 patients with advanced HCC with distant metastasis at initial diagnosis from June 2004 to June 2015. The patients received the first treatment for HCC in our hospital. Results: Mean age of patients was 57.3 ± 11.6 years and men were predominant (80.6%). The median observation period was 3.2 (0.3-39.1) months, and 99 (96.1%) of these patients died. There were no significant association with survival in sex, age, etiology and the number of liver tumors (p = 0.274, 0.094, 0.854 and 0.280, respectively). In univariate analysis, bilobar tumor distribution, invasion of main portal vein or IVC, Child-Pugh class, and treatment modality showed significant association with shorter survival. (p = 0.033, <0.001, 0.015, <0.001, and <0.001, respectively). In multivariate analysis, Child-Pugh class (p<0.001) and initial treatment modality (p=0.001) were significantly independent factors for survival. In Kaplan-Meier curve, systemic chemotherapy-alone or combination of locoregional treatment (LRT) and cytotoxic chemotherapy has no significant difference on survival compared with best supportive care as initial treatment. (median survival time, MST, 2.3 vs. 1.6 months) However, LRT alone (MST) or combination of sorafenib and LRT (MST 4.8, 4.3 months) showed significant survival benefit. (p = 0.001, 0.002). Conclusions: The Child-Pugh score and treatment modality in HCC patients with metastasis showed significant prognostic relevance. We also found that locoregional control for primary liver mass therapy is important in the treatment of sorafenib.

Efficacy and Safety in Genotype 1b HCV Infected Patients Who Are Treated by Ledipasvir/sofosbuvir: A Real Life and Multicenter Study

( Young Nam Kim ),( Sangheun Lee ),( Ki Jun Han ),( Seung Kak Shin ),( Oh Sang Kwon ),( Chang Hwi Yoon ),( Young-joo Jin ),( Jin-woo Lee ),( Tae Hun Kim ),( Yun Soo Kim ),( Duck Joo Choi ),( Ju Hyun K 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Background/Aim: Combination of ledipasvir (LDV)/sofosbuvir (SOF) ± ribavirin (RBV) has been approved in Korea for the treatment of genotype 1b (GT1b) hepatitis C virus (HCV) infected patients with NS5A resistance-associated variants (RAVs). The efficacy and safety were investigated in LDV/SOF±RBV treated patients. Methods: All HCV GT1b patients with NS5A RAV who were treated with LDV/SOF±RBV for at least 4 weeks from March 2016 to January 2017, were retrospectively enrolled from five hospitals. Virologic response was measured at 4 weeks (rapid virologic response, RVR), at 12 weeks (end of treatment response, ETR), and at 12 weeks after the end of treatment (sustained virologic response, SVR12). Safety was assessed by review of adverse events, physical examinations, and laboratory findings. Results: A total of 18 RAV-positive patients were treated with LDV/SOF±RBV at least 4 weeks [n=17, LDV/SOF; n= 1, LDV/SOF+RBV for treatment-experienced patients with liver cirrhosis (LC)]. Sixteen patients had Y93H variants and 2 patients had L31 plus Y93 double-substituted variants. Baseline characteristics were obtained: mean age (58±10 years), gender (male: 44.4%), LC (38.9%), treatment-naive (66.6%), mean AST (66.8±49.0 IU/L), mean ALT (66.2±36.8 IU/L), and mean HCV RNA level (2,789,457±5,007,723 IU/mL). Overall, RVR (14/16, 87.5%, HCV RNA was not checked in 2 patients at 4 weeks), ETR (9/9, 100 %), and SVR (5/5, 100 %) rates were obtained. Patients with SVR (n=5) included 3 patients with LC and 3 treatment-naive patients. There was no case of serious adverse events. Conclusions: LDV/SOF±RBV treatment for HCV GT1b infected Korean subjects with RAV achieved very high SVR rates.

Diagnosis of Suspicion: The Key to an Early Diagnosis of Fibrolamellar Hepatocellular Carcinoma

( Seung Woon Park ),( Soon Ho Um ),( Sun Young Yim ),( Tae Hyung Kim ),( Jemma Ahm ),( Eun Sun Kim ),( Bora Keum ),( Yeon Seok Seo ),( Yoon Tae Jeen ),( Hoon Jai Chun ),( Hong Sik Lee ),( Chang Duck K 대한내과학회 2015 대한내과학회 추계학술대회 Vol.2015 No.1

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare form of hepatocellular carcinoma. The prevalence in Korea remains to be clarified and a few cases are reported so far. It usually occurs in young people without underlying liver disease. Although it has distinct radiologic and histologic features, liver enzymes and serum Α-fetoprotein (AFP) have no significance leading to difficult early diagnosis. Clinicians should be aware of the possibility of FLHCC in young patient and dynamic image studies should be considered. A 21 year-old Korean man was admitted to department of hepatology due to newly developed right diaphragmatic elevation in chest X-ray. He complained of abdominal pain. His laboratory tests showed mild elevation of liver enzymes. Viral markerswere negative. The positive finding in tumor marker was elevated PIVKA-II. No elevation was observed in AFP. Hepatic lesion was suspected and imaging studies were performed. Chest computed tomography shows a enhancing hepatic mass with central calcifications (Fig. A). Liver magnetic resonance imaging with primovist shows a lobulated contoured mass with low signal intensity central scar, suggestive of FLHCC (Fig.B). He underwent liver resection. Microscopically, the cords of neoplastic hepatocytes were separated by parallel arrays of collagenous stroma, stained blue in Masson’s trichrome stain (Fig. C). The tumor cells had large, vesicular nuclei with prominent nucleoli and eosinophilic cytoplasm (Fig. D). It was diagnosed as FLHCC. No recurrence was observed during follow up.