Chun-Jen Liu

Publications (141)857.4 Total impact

• Article: Risk Stratification of Hepatocellular Carcinoma in Hepatitis B e Antigen-Negative Carriers by Combining Viral Biomarkers.

  Tai-Chung Tseng, Chun-Jen Liu, Chi-Ling Chen, Hung-Chih Yang, Tung-Hung Su, Chia-Chi Wang, Wan-Ting Yang, Stephanie Fang-Tzu Kuo, Chen-Hua Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: Background & Aims. Serum hepatitis B surface antigen (HBsAg) level can predict hepatocellular carcinoma (HCC) development in hepatitis B e antigen (HBeAg)-negative patients with HBV DNA level <2000 IU/mL. However, little is known regarding how well the combination of both viral biomarkers stratifies HCC risk.Methods. A total of 2165 Taiwanese HBeAg-negative non-cirrhotic patients were followed for 14.9 years. The predictive power of HBsAg level for HCC was analyzed for different viral load ranges.Results. In patients with HBV DNA level between 2000-19999 IU/mL (intermediate viral load), a positive correlation between HBsAg level and HCC development was identified after adjusting for other risk factors (P=.002). In contrast, no association was found between HBsAg level and HCC in patients with higher viral loads. HBsAg level was subsequently included to stratify HCC risk in patients with low and intermediate viral loads. Receiver operating characteristic curve analysis showed that combining HBV-DNA and HBsAg level better predicts 10-year HCC development compared to using HBV-DNA level alone in the overall cohort (P=.028).Conclusions. Serum HBsAg level helps stratify HCC risk in patients with intermediate viral loads. Combining HBV-DNA and HBsAg levels better predicts HCC risk.
  The Journal of Infectious Diseases 05/2013; · 6.41 Impact Factor
• Article: Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C.

  Tung-Hung Su, Chen-Hua Liu, Chun-Jen Liu, Chi-Ling Chen, Te-Tien Ting, Tai-Chung Tseng, Pei-Jer Chen, Jia-Horng Kao, Ding-Shinn Chen
  [show abstract] [hide abstract]
  ABSTRACT: MicroRNA-122 (miR-122) facilitates hepatitis C virus replication in vitro. Serum miR-122 has been implicated as a biomarker for various liver diseases; however, its role in chronic hepatitis C remains unclear. To address this issue, 126 patients with chronic hepatitis C who completed pegylated IFN plus ribavirin therapy with sustained virologic response (SVR) or nonresponse (NR) were retrospectively included, and their pretreatment clinical profiles and treatment responses were collected. Serum miR-122 was quantified before and during treatment. Another 51 patients in SVR and NR groups were prospectively enrolled for validation. Serum miR-122 was found to be a surrogate for hepatic miR-122 and positively correlated with hepatic necroinflammation. Patients who showed complete early virologic response and SVR had significantly higher pretreatment serum miR-122 levels than those with NR (P = 0.001 and P = 0.008, respectively), especially in subgroups of patients with hepatitis C virus genotype 2 and IL-28B rs8099917 TT genotype. Patients with IL-28B TT genotype had significantly better treatment responses and higher pretreatment serum miR-122 level than those with GT or GG genotypes. Univariate analysis showed that pretreatment body mass index, γ-glutamyl transpeptidase, triglyceride, IL-28B TT genotype, and serum miR-122 are predictors for SVR. Multivariate analysis specifically in IL-28B TT genotype demonstrated that pretreatment serum miR-122 independently predicted SVR. The validation cohort confirmed a significantly greater pretreatment serum miR-122 level in patients with SVR compared with NR (P = 0.025). In conclusion, serum miR-122 may serve as a surrogate of hepatic miR-122, and a higher pretreatment serum miR-122 level can help predict virologic responses to pegylated IFN plus ribavirin therapy.
  Proceedings of the National Academy of Sciences 04/2013; · 9.68 Impact Factor
• Article: Milder clinical manifestation of scrub typhus in Kinmen, Taiwan.

  Tung-Hung Su, Chun-Jen Liu, Ding-Shinn Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: Kinmen, an offshore island of Taiwan, is a popular location for sightseeing and an important entry port between Taiwan and China. Kinmen is also highly endemic for scrub typhus. The authors aimed to investigate the disease characteristics there, which remained largely unknown. The authors conducted a retrospective study on patients with scrub typhus in Kinmen during 2005-2008. The clinical information was reviewed from medical records for statistical analysis. There were 261 patients with scrub typhus included with a bimodal summer-autumn type of distribution, with most patients (40%) age 20-29 years and a large proportion of patients (26%) older than 60 years. The disease manifestation, laboratory examinations, and treatment outcomes were comparable in summer and autumn. Fever (97%), eschar (93%), and relative bradycardia (67%) were the most common presentations, whereas lymphadenopathy (18%) and skin rash (8%) were infrequent. Elevated liver function, C-reactive protein levels, and low to normal platelet counts were frequent findings. A correct diagnosis was made made in an average 3.7 days after fever or 1.6 visits of medical consultation, and minocycline was prescribed in a timely manner. Most patients had good recovery and only 12 patients (5%) had severe infection with acute renal failure, shock, gastrointestinal bleeding, or respiratory failure; no mortality was found. Older age, longer fever duration, thrombocytopenia, abnormal liver and renal function, hyponatremia, and elevated C-reactive protein levels were significantly associated with severe complications and prolonged treatment duration. A unique summer-autumn type of scrub typhus with milder disease manifestations is identified in Kinmen. The younger patient population, rapid diagnosis, and prompt treatment may be associated with a shortened disease course and lead to a better outcome.
  Journal of the Formosan Medical Association 04/2013; 112(4):201-7. · 1.13 Impact Factor
• Article: Sustained hcv clearance and increased HBsAg seroclearance in patients with dual chronic hepatitis C and B during post-treatment follow-up.

  Ming-Lung Yu, Chuan-Mo Lee, Chi-Ling Chen, Wan-Long Chuang, Sheng-Nan Lu, Chen-Hua Liu, Shun-Sheng Wu, Li-Ying Liao, Hsing-Tao Kuo, You-Chen Chao, Shui-Yi Tung, Sien-Sing Yang, Jia-Horng Kao, Wei-Wen Su, Chih-Lin Lin, Hung-Chih Yang, Pei-Jer Chen, Ding-Shinn Chen, Chun-Jen Liu
  [show abstract] [hide abstract]
  ABSTRACT: Patients dually infected with hepatitis C virus (HCV)/hepatitis B virus (HBV) have a higher risk of developing advanced liver disease or hepatocellular carcinoma compared to monoinfected patients. Our previous study showed a similar rate of sustained virologic response (SVR) after peginterferon alfa-2a and ribavirin combination therapy in these patients compared to HCV monoinfected patients, and a high hepatitis B surface antigen (HBsAg) seroclearance rate. The durability of hepatitis C and B clearance in dually infected patients was investigated by a 5-year follow-up study. Patients with active HCV genotype 1, both HBV coinfected (n=97) and monoinfected (n=110), received a 48-week combination therapy with peginterferon alfa-2a plus ribavirin. Patients with active HCV genotype 2/3, both HBV coinfected (n=64) and monoinfected (n=50) patients received a 24-week combination therapy. A total of 295 (91.9%) patients completed treatment and 24 weeks post-treatment follow-up; 264 (89.5%) agreed to receive additional follow-up for up to 5 years after the end of treatment. After a median follow-up of 4.6 + 1.0 years, 6 of the 232 patients achieving SVR developed HCV RNA reappearance, including 5 HCV genotype 1/HBV coinfected patients and 1 HCV genotype 2/3 monoinfected patient. Subgenomic analysis of the HCV core gene suggested that 5 patients developed delayed recurrence of HCV infection. Overall, the cumulative recurrence rate of HCV infection was 2.3% (0.4%/year; 95% confidence interval [CI]=0.9%∼5.5%). The cumulative HBsAg seroclearance rate was 30.0% (95% CI=21.5%∼42.0%); with 33.1% (95% CI=21.8%∼50.1%) in 48-week combination therapy group and 24.3% (95% CI=13.7%∼42.9%) in 24-week therapy group. Conclusion: Peginterferon alfa-2a and ribavirin therapy provides a good durability of HCV SVR and a high accumulative HBsAg seroclearance rate in patients dually infected with HCV and HBV. (HEPATOLOGY 2013.).
  Hepatology 01/2013; · 11.66 Impact Factor
• Article: IL-21R gene polymorphisms and serum IL-21 levels predict virological response to interferon-based therapy in Asian chronic hepatitis C patients.

  Ching-Sheng Hsu, Shih-Jer Hsu, Wei-Liang Liu, Chen-Hua Liu, Chi-Ling Chen, Chun-Jen Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: IL-21R polymorphisms have been identified as potential predictors of virologic outcomes in Western chronic hepatitis C (CHC) patients receiving interferon-based treatment. We aimed to examine the associations of IL-21R genotypes and serum IL-21 levels with virologic responses to interferon-based treatment in Asian CHC patients. METHODS: Genomic and clinical data were collected from 178 consecutive Taiwanese HCV genotype 1 patients who received interferon-based therapy and 72 non-HCV healthy subjects. Among them, serum IL-21 levels, IL-21R and IL28B genotypes were determined in 124 CHC patients and healthy controls. RESULTS: Among patients with IL28B rs8099917 non-TT genotypes, patients with IL-21R rs3093390 CC genotype had a higher SVR rate than those with non-CC genotypes (CC vs. non-CC: 14/24 vs. 0/4, P=0.031). Compared to non-HCV controls, CHC patients had higher serum IL-21 levels [HCV vs. non-HCV: 377.8±780.9 vs. 70.5±33.2(pg/mL), P=0.001]. Patients with SVR had higher pretreatment serum IL-21 levels than those without (Adjusted Odds Ratio, 95%CI: 0.23, 0.07-0.80, P=0.021). CONCLUSIONS: CHC patients have higher serum IL-21 levels than healthy adults. Higher pretreatment serum IL-21 levels and IL-21R polymorphisms may serve as potential factors predictive of treatment outcomes in CHC patients with interferon-based therapy.
  Antiviral therapy 01/2013; · 3.16 Impact Factor
• Article: Host Genetic Factors Affecting Spontaneous HBsAg Seroclearance in Chronic Hepatitis B Patients.

  Huei-Ru Cheng, Chun-Jen Liu, Tai-Chung Tseng, Tung-Hung Su, Hwai-I Yang, Chien-Jen Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: Spontaneous clearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients usually indicates a remission of hepatitis activity and a favorable outcome. Two single nucleotide polymorphisms (SNP), rs3077 near HLA-DPA1 region and rs9277535 near HLA-DPB1 region, have been shown to be associated with HBV persistence after acute HBV infection. However, little is known about the impact of these 2 SNPs on spontaneous HBsAg clearance in CHB patients. In this case-control study, a total of 100 male HBeAg-negative chronic HBV carriers who cleared HBsAg spontaneously (case group) and 100 age-matched HBeAg-negative male patients with persistent HBsAg positivity (control group) were enrolled. We investigated the relationship between these 2 SNPs and HBsAg clearance. There was a higher frequency of rs9277535 non-GG genotype in the case group (57% vs. 42%). Patients with rs9277535 non-GG genotype had a higher chance to clear HBsAg [Odds ratio (OR): 1.83, 95% confidence interval (CI): 1.04∼3.21, P = 0.034]. Compared to GG haplotype of rs3077 and rs9277535, GA haplotype had a higher chance of achieving spontaneous HBsAg loss (OR: 2.17, 95% CI: 1.14∼4.16, P = 0.030). In conclusion, rs9277535 non-GG genotype is associated with a higher likelihood of spontaneous HBsAg seroclearance in CHB patients.
  PLoS ONE 01/2013; 8(1):e53008. · 4.09 Impact Factor
• Article: Longitudinal Change of HBsAg in HBeAg-negative Patients with Genotype B or C Infection.

  Tung-Hung Su, Chun-Jen Liu, Tai-Chung Tseng, Chen-Hua Liu, Hung-Chih Yang, Chi-Ling Chen, Pei-Jer Chen, Jia-Horng Kao, Ding-Shinn Chen
  [show abstract] [hide abstract]
  ABSTRACT: Quantitative HBsAg has been recognized to assist in the management of chronic hepatitis B virus (HBV) infection. However, its role in disease monitoring of HBeAg-negative patients remains unclear. We aimed to investigate the longitudinal HBsAg change in HBeAg-negative carriers with HBV genotype B or C infection. This is a retrospective cohort study conducted in a university hospital. Treatment-naïve HBeAg-negative carriers followed for more than 3 years were recruited. Their hepatitis activities were categorized by longitudinal HBV-DNA levels into high viral-load (HVL: HBV-DNA >/ = 2000 IU/mL persistently), low viral-load (LVL: HBV-DNA <2000 IU/mL persistently) and fluctuated viral-load (FVL: HBV-DNA between HVL and LVL). The baseline and end-of-follow-up (EOF) HBsAg levels were quantified for analyses. We recruited 187 patients with a median follow-up of 8 years. LVL patients had a significantly lower HBsAg at baseline and EOF and a significantly greater annualized HBsAg decline compared with the FVL and HVL. The longitudinal HBsAg change was independent of genotype B or C. The lower baseline HBsAg level predicted the HBsAg decline and HBsAg loss, whereas the higher baseline HBV-DNA predicted the hepatitis flare. A baseline HBsAg <50 IU/mL predicted subsequent HBsAg loss with a sensitivity of 82% and specificity of 67%. The annualized HBsAg decline appeared non-linear, and accelerated as the HBsAg level lowered (0.054, 0.091, 0.126 log(10) IU/mL in patients with baseline HBsAg >1000, 100-999, <100 IU/mL, respectively, P for trend = .014). In genotype B or C HBeAg-negative carriers, baseline HBsAg levels correlate with future disease activities and help to predict HBsAg decline or loss. Inactive carriers with lower baseline HBsAg levels have a greater and accelerating HBsAg decline over time, regardless of HBV genotypes.
  PLoS ONE 01/2013; 8(2):e55916. · 4.09 Impact Factor
• Article: Distinct evolution and predictive value of hepatitis B virus precore and basal core promoter mutations in interferon-induced HBeAg seroconversion.

  Hung-Chih Yang, Chi-Ling Chen, Yueh-Chi Shen, Cheng-Yuan Peng, Chun-Jen Liu, Tai-Chung Tseng, Tung-Hung Su, Wan-Long Chuang, Ming-Lung Yu, Chia-Yen Dai, Chen-Hua Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: Precore (PC) (G1896A) and basal core promoter (BCP) (A1762T/G1764A) mutations of hepatitis B virus (HBV) genome often emerge in chronic hepatitis B (CHB) patients. Their roles in HBeAg seroconversion induced by interferon therapy remain controversial, partly because quantitative analysis for these mutants is lacking. This study aimed to develop a new assay to accurately quantify the PC and BCP mutant percentages and correlate their dynamic changes with interferon-induced HBeAg seroconversion in HBeAg-positive CHB patients. The PC and BCP mutant percentages were analyzed by PCR-pyrosequencing. Our results showed this quantitative assay for PC and BCP mutants achieved high accuracy (R(2) >0.99) within a range between 10% and 90% mutants. We examined dynamic changes of the PC and BCP mutant percentages following interferon treatment in 203 HBeAg-positive CHB patients. By multiple logistic regression analysis, we found that the chance of HBeAg seroconversion increased by 2.2% (OR=1.022, 95% CI: 1.009-1.034, P=0.001) and 2.3% (OR=1.023, 95% CI: 1.010-1.037, P =0.001) per 1% increase of the pretreatment PC and BCP mutant percentages, respectively, after adjustment for other predictors. However, only the pretreatment PC mutation percentage was significantly associated with HBeAg seroconversion with HBV DNA < 2,000 IU/mL (OR= 1.030, 95% CI: 1.014-1.047, P<0.001) . Furthermore, the mutant percentage of PC, but not BCP, in patients achieving HBeAg seroclearance with HBV DNA < 20,000 IU/mL increased significantly during interferon treatment (P=0.039). Interestingly, patients with HBeAg seroconversion who had a high PC mutant percentage at the end of interferon treatment tended to exhibit high viremia after seroconversion. Conclusion: Quantitative analysis of PC and BCP mutants can predict interferon-induced HBeAg seroconversion and demonstrate their distinct evolution patterns during HBeAg seroconversion. (HEPATOLOGY 2012.).
  Hepatology 10/2012; · 11.66 Impact Factor
• Article: Young Chronic Hepatitis B Patients With Nucleos(t)ide Analogue-induced Hepatitis B e Antigen Seroconversion Have a Higher Risk of HBV Reactivation.

  Tai-Chung Tseng, Chun-Jen Liu, Tung-Hung Su, Hung-Chih Yang, Chia-Chi Wang, Chi-Ling Chen, Stephanie Fang-Tzu Kuo, Chen-Hua Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: Background. It is unclear whether hepatitis B e antigen (HBeAg) seroconversion induced by nucleos(t)ide analogues (NUC) has a prognosis that is similar to that of spontaneous HBeAg seroconversion. Methods. A total of 148 noncirrhotic NUC-induced HBeAg seroconverters were consecutively enrolled. A historical control of 407 noncirrhotic spontaneous HBeAg seroconverters was also recruited. We compared the rates of HBeAg seroreversion and HBV reactivation between these 2 cohorts. Results. There were 1652.8 and 465.2 person-years of follow-up for spontaneous and NUC-induced HBeAg seroconverters, respectively. Compared with NUC-induced seroconverters, spontaneous seroconverters were younger when achieving HBeAg seroconversion. We thus compared these 2 cohorts according to their age at HBeAg seroconversion. In patients achieving HBeAg seroconversion before 30 years of age, NUC-induced seroconverters had a higher 2-year HBeAg seroreversion rate than spontaneous seroconverters (12.0% vs 2.9%; P = .004) and were at a higher risk of HBV reactivation (hazard ratio, 4.6; 95% confidence interval, 1.5-14.4). Using multivariate analysis, NUC-induced HBeAg seroconversion remained a risk factor of both endpoints in young HBeAg seroconverters. Conclusion. NUC-induced HBeAg seroconverters may not have durable response after stopping therapy. For patients achieving HBeAg seroconversion before 30 years of age, the risk of HBeAg seroreversion and HBV reactivation is higher in NUC-induced seroconverters than spontaneous HBeAg seroconverters.
  The Journal of Infectious Diseases 09/2012; 206(10):1521-31. · 6.41 Impact Factor
• Source

  Available from: Ching-Sheng Hsu

  Dataset: JGH 2010 HCV Fibrosis MS

  Ching-Sheng Hsu, Chen-Hua Liu, Chun-Jen Liu, Shih-Jer Hsu, Chi-Ling Chen, Juey-Jen Hwang, Ming-Yang Lai, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
• Source

  Available from: Ching-Sheng Hsu

  Dataset: HI 2010 GERD HBV

  Ching-Sheng Hsu, Chia-Chi Wang, Pin-Chao Wang, Hans Hsienhong Lin, Tai-Chung Tseng, Chien-Hwa Chen, Wei-Chih Su, Chun-Jen Liu, Chi-Ling Chen, Ming-Yang Lai, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
• Article: Serum hepatitis B surface antigen levels help predict disease progression in patients with low HBV loads.

  Tai-Chung Tseng, Chun-Jen Liu, Hung-Chih Yang, Tung-Hung Su, Chia-Chi Wang, Chi-Ling Chen, Cheng-An Hsu, Stephanie Fang-Tzu Kuo, Chen-Hua Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND & AIMS: Chronic hepatitis B patients with high viral loads are at increased risk of cirrhosis and hepatocellular carcinoma (HCC). In those with low viral loads, higher hepatitis B surface antigen (HBsAg) levels have been shown to predict HCC development. However, little is known about the difference in risk for other hepatitis B virus (HBV)-related adverse outcomes with varying HBsAg levels. METHODS: A total of 1068 Taiwanese hepatitis B e antigen (HBeAg)-negative HBV carriers with serum HBV DNA level <2000 IU/mL at baseline were followed for a mean duration of 13.0 years. Patients were categorized based on their HBsAg levels, and the relationships between HBsAg level and development of HBeAg-negative hepatitis, hepatitis flare, and cirrhosis were investigated. RESULTS: Of the 1068 patients with low viral loads, 280 developed HBeAg-negative hepatitis with an annual incidence rate of 2.0%. HBsAg level, but not HBV DNA level, was found to be a risk factor for HBeAg-negative hepatitis. Multivariate analysis showed that the adjusted hazard ratio in patients with HBsAg level ≧1000 versus <1000 IU/mL was 1.5 (95% confidence interval, 1.2-1.9). The positive correlation was present when evaluating other endpoints, including hepatitis flare and cirrhosis, and remained consistent when the study population was restricted to those with normal alanine aminotransferase (ALT) level at baseline. The annual incidence rate of HBeAg-negative hepatitis was lowered to 1.1% in those with low levels of HBV DNA, HBsAg, and ALT. CONCLUSIONS: In HBeAg-negative patients with low viral loads and genotype B or C virus infection, a higher HBsAg level can predict disease progression. HBsAg <1000 IU/mL in combination with low levels of HBV DNA and ALT help define minimal-risk HBV carriers. (HEPATOLOGY 2012.).
  Hepatology 09/2012; · 11.66 Impact Factor
• Article: Identification of a liver cirrhosis signature in plasma for predicting hepatocellular carcinoma risk in a population-based cohort of hepatitis B carriers.

  Chia-Chi Liu, Ya-Hui Wang, Eric Y Chuang, Mong-Hsun Tsai, Ya-Hui Chuang, Chih-Lin Lin, Chun-Jen Liu, Bo-Yu Hsiao, Shi-Ming Lin, Li-Yu Liu, Ming-Whei Yu
  [show abstract] [hide abstract]
  ABSTRACT: Liver cirrhosis is a critical state in the natural course of hepatocellular carcinoma (HCC). We sought to investigate the potential of in-depth proteomics to reveal plasma protein signatures that reflect common networks/pathways of liver cirrhosis, and to determine whether the cirrhosis-related signature in plasma is linked to the development of HCC among hepatitis B virus (HBV) carriers. We first compared plasma protein profiles using a 174-antibody microarray system between three groups of HBV carriers with different Child's grades of cirrhosis, which revealed a panel of 45 differentially expressed proteins with a high accuracy for discriminating Child's B/C. Ingenuity Pathway Analysis identified two main up-regulated networks connecting the 45 proteins that were most enriched for genes in the pathway of hepatic stellate cell activation. A parsimonious subset of 11 pathway-based proteins was then selected for quantification to correlate with HCC risk among 49 HCC cases and 50 controls in a nested case-control study within a 16-yr follow-up cohort of HBV carriers. A high risk score derived from a principal component analysis, which was used to extract the cluster structure of the 11 proteins, was associated with HCC (odds ratio = 4.83, 95% confidence interval: 1.26-18.56) even after adjustment for viral and clinical variables, implying the involvement of a pattern of coordinated proteins. Stepwise logistic regression on the 11 proteins revealed ICAM-2 as an independent predictor for HCC. These findings may give further insight into the pathobiology of hepatocarcinogenesis, allow testing of the cirrhosis-related plasma protein signature as a potential predictive biomarker for HCC. © 2012 Wiley Periodicals, Inc.
  Molecular Carcinogenesis 08/2012; · 3.16 Impact Factor
• Article: Interleukin 28B genetic polymorphisms play a minor role in identifying optimal treatment duration in HCV genotype 1 slow responders to pegylated interferon plus ribavirin.

  Chen-Hua Liu, Cheng-Chao Liang, Chun-Jen Liu, Tai-Chung Tseng, Chih-Lin Lin, Sheng-Shun Yang, Tung-Hung Su, Jou-Wei Lin, Jun-Herng Chen, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: Pegylated interferon and ribavirin for 72 weeks improve sustained virological response (SVR) in HCV genotype 1 (HCV-1) slow viral responders. Whether interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and on-treatment viral responses can identify non-rapid virological response (RVR) patients who benefit from 48 or 72 weeks of therapy remains unclear. Treatment-naive HCV-1 patients who failed to achieve RVR were randomly assigned to receive 48 (n=168) or 72 (n=167) weeks of therapy. Baseline factors and on-treatment virological responses at weeks 8 and 12 were evaluated for SVR in 289 compliant patients who received ≥80% of drug dosages and treatment duration, and had end of follow-up viral response. The stratified SVR rates for independent factors were compared by treatment duration. Treatment duration, IL28B rs8099917 genotypes, cirrhosis, week-8 viral response (undetectable HCV RNA at treatment week 8) and complete early virological response (cEVR) predicted SVR. In week-8 viral response patients, the SVR rates of 72-week and 48-week treatment were similar (75-88%), regardless of IL28B SNP genotypes or cirrhosis. In non-week-8 viral response patients who achieved cEVR, the SVR rate of 72-week treatment was higher than that of 48-week treatment for non-cirrhotic patients, regardless of IL28B SNP genotypes (91-100% versus 13-44%; P=0.001). Although IL28B SNP genotypes predict SVR, they play a minor role when on-treatment viral responses are taken into consideration. On-treatment viral responses at weeks 8 and 12 are the key determinants to decide the optimal treatment duration in HCV-1 patients without RVR.
  Antiviral therapy 08/2012; 17(6):1059-67. · 3.16 Impact Factor
• Article: Quantitative hepatitis B core antibody level may help predict treatment response in chronic hepatitis B patients.

  Quan Yuan, Liu-Wei Song, Chun-Jen Liu, Zhuo Li, Ping-Guo Liu, Cheng-Hao Huang, Yan Yan, Sheng-Xiang Ge, Ying-Bin Wang, Cheng-Yuan Peng, Jun Zhang, Jia-Horng Kao, Ding-Shinn Chen, Pei-Jer Chen, Ning-Shao Xia
  Gut 06/2012; · 10.11 Impact Factor
• Article: Fine mapping of hepatitis B virus pre-S deletion and its association with hepatocellular carcinoma.

  Jia-Horng Kao, Chun-Jen Liu, Guey-Mei Jow, Pei-Jer Chen, Ding-Shinn Chen, Bing-Fang Chen
  [show abstract] [hide abstract]
  ABSTRACT: Naturally occurring pre-S deletion mutants have been identified in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study investigated whether specific deletions within the pre-S region were associated with HCC development. The virologic characteristics of 56 HBV chronic carriers and 112 age-matched patients with HBV-related HCC were examined. The HCC patients had a significantly higher frequency of high viral load, basal core promoter mutation and pre-S deletion than chronic carriers. Sequencing analysis showed that the deleted regions were clustered mainly in the C terminus of pre-S1 (70.5%) and the N terminus of pre-S2 (72.7%) in HCC patients. Immuno-epitope mapping of these pre-S deletion sequences showed that all the deletion regions encompassed T- and B- cell epitopes and the B-cell epitope at amino acid 1-6 of pre-S2 was significantly deleted in HCC patients (60.0% vs. 0.0%; P = 0.036). Functional mapping of these deletion mutants showed that most of HCC patients lost one or more functional sites and the deletion of site for viral secretion (aa 1-5 of pre-S2 domain) was significantly detected in HCC patients than chronic carriers (62.5% vs. 0.0%; P = 0.029). Computational protein function prediction indicated that these mutants may have different molecular functions and participate in other biological processes compared with wild-type pre-S. Deletion of B-cell epitope at amino acid 1-6 of pre-S2 region and the site for virion secretion are significantly associated with the development of HCC in HBV carriers.
  Liver international: official journal of the International Association for the Study of the Liver 06/2012; 32(9):1373-81. · 3.82 Impact Factor
• Article: Influences of tobacco and alcohol use on hepatocellular carcinoma survival.

  Wei-Liang Shih, Hung-Chuen Chang, Yun-Fan Liaw, Shi-Ming Lin, Shou-Dong Lee, Pei-Jer Chen, Chun-Jen Liu, Chih-Lin Lin, Ming-Whei Yu
  [show abstract] [hide abstract]
  ABSTRACT: Prognosis of hepatocellular carcinoma (HCC) is generally poor. The role of modifiable lifestyle factors on HCC survival has been less studied. To examine whether prediagnosis smoking and alcohol affected HCC survival stratified by viral etiology, we conducted a prospective cohort study of 2,273 (1990 with viral hepatitis and 283 without) incident HCC cases aged 20-75 years who were enrolled between 1997 and 2004 from a Taiwanese multicenter study, and followed up through 2007. Information on habitual smoking and alcohol consumption was obtained at baseline through personal interview. After follow-up to a maximum of 10 years, 1,757 participants died and 1,488 (84.7%) were attributed to HCC. Prediagnosis smoking and alcohol worsened prognosis independent of each other and clinical predictors. The effects of both risky behaviors were limited to viral hepatitis-related HCC and more profound among those with early-stage HCC. Risk for HCC-specific mortality increased with increasing pack-years smoked and ethanol intake (all p < 0.001 for trend), with an additive effect shown for the two habits [hazard ratio (HR) for alcohol ≥46.2 g/day and ≥10 pack-years = 1.72, 95% confidence interval (CI) = 1.45-2.05]. For either habit, cessation reduced HCC-specific mortality, but a significant mortality benefit occurred 10 years after abstinence (quitting smoking ≥10 years vs. continuing smokers: HR = 0.77, 95% CI = 0.61-0.97; quitting drinking ≥10 years vs. continuing drinkers: HR = 0.74, 95% CI = 0.56-0.98). In conclusion, among patients with viral hepatitis-related HCC, prediagnosis smoking and alcohol have a deleterious effect on HCC survival. Quitting smoking or drinking alcohol could reduce the excess risk, but only after a long interval of cessation.
  International Journal of Cancer 02/2012; 131(11):2612-21. · 5.44 Impact Factor
• Article: High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load.

  Tai-Chung Tseng, Chun-Jen Liu, Hung-Chih Yang, Tung-Hung Su, Chia-Chi Wang, Chi-Ling Chen, Stephanie Fang-Tzu Kuo, Chen-Hua Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: Patients with chronic hepatitis B virus (HBV) infection have a high risk for developing hepatocellular carcinoma (HCC). Patients with lower levels of hepatitis B surface antigen (HBsAg) have higher chances of losing HBsAg than those with high levels. However, little is known about whether higher levels of HBsAg increase risk for HCC. We followed 2688 Taiwanese HBsAg-positive patients without evidence of cirrhosis for a mean time period of 14.7 years. In addition to the known risk factors of HCC, we investigated the association between levels of HBsAg and development of HCC. Of the patients followed, 191 developed HCC, with an average annual incidence rate of 0.5%. Baseline levels of HBsAg and HBV were associated with development of HCC, and risk increased with level. Compared to HBsAg level, by receiver operating characteristic curve analysis, HBV DNA level better predicted the development of HCC during 10-year and 15-year periods (both, P < .001). However, when we evaluated hepatitis B e antigen-negative patients with levels of HBV DNA <2000 IU/mL, factors that determined HCC risk included sex, age, and levels of alanine aminotransferase and HBsAg (≥1000 IU/mL), but not level of HBV DNA. Multivariate analysis showed that the adjusted hazard ratio for HCC in patients with levels of HBsAg ≥1000 IU/mL versus <1000 IU/mL was 13.7 (95% confidence interval: 4.8-39.3). Among patients infected with HBV genotype B or C, determinants of HCC risk include their sex, age, hepatitis B e antigen status, HBV genotype, and levels of alanine aminotransferase and HBV DNA, but not level of HBsAg. Among hepatitis B e antigen-negative patients with low viral loads, HCC risk is determined by levels of HBsAg and alanine aminotransferase and age, but not HBV DNA.
  Gastroenterology 02/2012; 142(5):1140-1149.e3; quiz e13-4. · 11.68 Impact Factor
• Source

  Available from: Ching-Sheng Hsu

  Article: Association of IL28B genotypes with metabolic profiles and viral clearance rate in chronic hepatitis C patients

  Ching-Sheng Hsu, Shih-Jer Hsu, Hung-Chia Chen, Chen-Hua Liu, Jenher Jeng, Chun-Jen Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
  Hepatology International 01/2012; · 2.64 Impact Factor
• Article: Interleukin 28B genetic polymorphisms and viral factors help identify HCV genotype-1 patients who benefit from 24-week pegylated interferon plus ribavirin therapy.

  Chen-Hua Liu, Cheng-Chao Liang, Chun-Jen Liu, Tai-Chung Tseng, Chih-Lin Lin, Sheng-Shun Yang, Tung-Hung Su, Shih-Jer Hsu, Jou-Wei Lin, Jun-Herng Chen, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
  [show abstract] [hide abstract]
  ABSTRACT: Interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and viral factors can predict sustained virological response (SVR) in HCV genotype-1 (HCV-1) patients receiving 48 weeks of pegylated interferon and ribavirin. Whether these factors would identify those patients who can benefit from a shorter duration of therapy remains unclear. Treatment-naive HCV-1 patients (n=662) receiving 24 or 48 weeks of combination therapy were enrolled. Baseline demographic data, HCV viral load, IL28B SNP genotypes (rs8099917), duration of therapy and rapid virological response (RVR) were evaluated to predict SVR. The SVR rates were further stratified by the independent factors and compared. The IL28B rs8099917 TT genotype, low baseline viral load (HCV RNA≤600,000 IU/ml), RVR and 48-week therapy independently predicted SVR. In RVR patients with the IL28B rs8099917 TT genotype, the SVR rate of 24-week therapy was comparable to 48-week therapy (95% versus 99%; P=0.21) at low baseline viral load, but was inferior to 48-week therapy (70% versus 97%; P<0.001) at high baseline viral load. In non-RVR patients, the SVR rate of 24-week therapy was inferior to 48-week therapy for those with the IL28B rs8099917 TT genotype but high baseline viral load (23% versus 62%; P<0.001), and those with the IL28B rs8099917 GT/GG genotype but low baseline viral load (0% versus 33%; P=0.02). HCV-1 patients simultaneously bearing the IL28B rs8099917 TT genotype, low baseline viral load and RVR can benefit from a shorter duration of combination therapy.
  Antiviral therapy 12/2011; 17(3):477-84. · 3.16 Impact Factor