Sheng-Nan Lu

National Cheng Kung University, 臺南市, Taiwan, Taiwan

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Publications (237)1111.12 Total impact

  • Shin-Yu Lu · Chi-Yu Tsai · Sheng-Nan Lu · Liang-Ho Lin ·
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    ABSTRACT: Most Western studies do not recommend interrupting warfarin therapy or replacing it with heparin prior to tooth extraction if the international normalized ratio (INR) levels are maintained. However, this issue remains controversial in Taiwan. The aim of this study was to investigate whether Taiwanese patients who had an INR within the therapeutic range required cessation of warfarin prior to dental extractions.
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    ABSTRACT: We investigated the rate of relapse of hepatitis B virus (HBV) infection after entecavir therapy for chronic hepatitis B and the association between level of hepatitis B surface antigen (HBsAg) and relapse. In a retrospective study, we analyzed data from 252 patients with chronic HBV infection who were treated with entecavir and met the Asian Pacific Association for the Study of the Liver treatment stopping rules (mean time, 164±45 weeks), from January 2007 through June 2011 in Taiwan. Eighty-three were hepatitis B e antigen (HBeAg)-positive and 169 were HBeAg-negative. Patients had regular post-treatment follow-up examinations for at least 12 months. Virologic relapse was defined based on serum HBV-DNA >2000 IU/mL after entecavir therapy. Clinical relapse was defined as a level of alanine aminotransferase >2-fold the upper limit of normal and HBV-DNA>2000 IU/mL. Two years after therapy ended, 42% of HBeAg-positive patients had a virologic relapse and 37.6% had a clinical relapse; 3 years after therapy ended these rates were 64.3% and 51.6%, respectively. Based on Cox regression analysis, factors independently associated with virologic and clinical relapse included old age, HBV genotype C, and higher baseline levels of HBsAg for HBeAg-positive patients, and old age and higher end-of-treatment levels of HBsAg for HBeAg-negative patients. In HBeAg-positive patients, risk of HBV relapse increased with age ≥40 years and HBsAg level ≥1000 IU/mL at baseline (P<.001). In HBeAg-negative patients, the combination of age (<55 years) and HBsAg level (<150 IU/mL) at the end of treatment was associated with a lower rate of virologic relapse (4.5% of HBeAg-negative patients had viral relapse at year 3). The decreased in level of HBsAg from month 12 of treatment until the end of treatment was greater in patients who did lose HBsAg after entecavir therapy compared to those who did not. The combination of age and level of HBsAg are associated with relapse of HBV infection following treatment with entecavir. HBsAg levels might be used to guide the timing of cessation of entecavir treatment in patients with chronic HBV infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 06/2015; DOI:10.1016/j.cgh.2015.06.002 · 7.90 Impact Factor
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    ABSTRACT: This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (TDF), telbivudine (LdT), and entecavir (ETV). We performed a retrospective study of 587 CHB patients treated with TDF (n = 170), LdT (n = 184) and ETV (n = 233) at least for 1 year. Renal function and efficacy were assessed. The eGFR decreased significantly in the TDF group after a mean of 17 months treatment (92.2 → 85.6 ml/min/1.73m(2), p <0.001), but increased in the LdT group after a mean of 32 months treatment (86.1 → 95 ml/min/1.73m(2), p <0.001). There was no significant change in eGFR in the ETV group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), TDF (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virologic breakthrough was 0% in TDF after 2 years, 3.4% in ETV after 7 years and 22.9% in LdT after 5 years. Liver cirrhosis (p = 0.008) and virologic breakthrough (p = 0.040) were independently associated with increase risk of HCC development. TDF may lead to deterioration in renal function as assessed by serial eGFR measurements. Although LdT appeared to be associated with an improvement in eGFR, it was associated with high rates of virologic breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, ETV could be the best choice among these 3 agents. Copyright © 2015. Published by Elsevier Ltd.
    Clinical Microbiology and Infection 06/2015; DOI:10.1016/j.cmi.2015.05.035 · 5.77 Impact Factor
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    ABSTRACT: To elucidate the results of post-screening care stratagems for anti-hepatitis C virus (HCV)-positive subjects in the community. Part I methods: The intervention program: A total of 151,790 subjects underwent a large-scale healthcare screening. Subjects aged less than 65 years, with anti-HCV-positive and alanine aminotransferase (ALT) level more than 80 IU/L were followed-up to answer a structured questionnaire. Those responders who met the reimbursement criteria of Taiwan's National Health Insurance for anti-HCV treatment were referred for treatment. Part II: The accessible medical care program: In Yujing township, 271 HCV residents who have been screened before were invited to a bi-weekly hepatitis clinic in Yujing health center. Part-I results: A total of 907 anti-HCV-positive subjects responded and 197(21.7%) were advised the treatment, but only 83(9.2%) did. Finally, 47 patients achieved a sustained virological response (SVR). After this intervention program, 96(10.6%) additional patients were encouraged to be referred, 33(3.6%) received treatment and 20 obtained a SVR. Part II: A total of 140(51.7%) subjects responded and 112 were anti-HCV-positive including 31(27.7%) HCV RNA-negative, 49(43.8%) HCV RNA-positive plus ALT less than 40 IU/L and 32(28.5%) HCV RNA-positive plus ALT more than 40 IU/L. During the follow-up, 14 of 49 patients had ALT more than 40 IU/L. Among 46 eligible HCV patients, 15(32.6%) received treatment and 10 achieved a SVR. Simple notification only made 9.2% of the screened HCV patients treat. Active referral could encourage additional 3.6% to be treated. Additionally, accessible medical care program could result in treatment of 32.6% elderly eligible patients.
    PLoS ONE 05/2015; 10(5):e0126031. DOI:10.1371/journal.pone.0126031 · 3.23 Impact Factor
  • Yuan-Hung Kuo · Sheng-Nan Lu ·

    The Kaohsiung journal of medical sciences 05/2015; 31(7). DOI:10.1016/j.kjms.2015.04.003 · 0.80 Impact Factor
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    ABSTRACT: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are effective antivirals recommended as first-line monotherapies for chronic hepatitis B (CHB). This study aimed to compare the short-term efficacy between TDF and ETV in the treatment of CHB with severe acute exacerbation. From 2008 to 2013, 189 consecutive treatment-naïve CHB patients receiving TDF (n=41) or ETV (n=148) for severe acute exacerbation were enrolled. The primary endpoint was overall mortality or receiving liver transplantation by week 24. The baseline characteristics were comparable between these two groups. By week 24, eight (19%, 95% confidence interval (CI):7%-32%) patients in the TDF group and twenty-six (18% (11-24%)) patients in the ETV group died (n=30) or received liver transplantation (n=4) (p=0.749). Both groups of patients developed similar rates of liver-related complications, and achieved comparable biochemical and virological response at week 24. Cox regression analysis showed that baseline viral DNA level (p=0.002), hypertension (p=0.002), model for end-stage liver disease (MELD) score (p=0.01), platelet count (p=0.005), early presence (within 4 weeks) of ascites (p=0.005), hepatic encephalopathy (p=0.002) and hepatorenal syndrome (p<0.001) were independent factors for mortality or liver transplantation. Among patients who survived by week 24, there was no difference in serum creatinine increase≥0.5 mg/dL from baseline between two groups (6.7% (0%-16%) vs. 2.0% (0%-4.8%), p=0.231), whereas significant reduction of estimated glomerular filtration rate (eGFR) was found in both groups (p=0.001 and p=0.001, respectively). In conclusion, TDF and ETV produce similar treatment response and clinical outcomes in patients with severe acute exacerbation of CHB. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 03/2015; 59(6). DOI:10.1128/AAC.00261-15 · 4.48 Impact Factor
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    ABSTRACT: This study was to elucidate longitudinally quantitative changes of hepatitis B virus (HBV) surface antigen (HBsAg) and HBV DNA in elder HBsAg carriers in a community. Among 1002 residents screened for HBsAg in 2005, 405 responded to this follow-up study in 2010. Fifty-nine (14.6%) were HBsAg carriers in 2005; HBsAg quantification and HBV DNA were measured. HBsAg quantification (cutoff 1600 IU/mL) and HBV DNA (cutoff 2000 IU/mL) were combined to stratify the participants between two screens. A total of 30 men and 29 women with a mean age of 63.9 ± 7.9 years were enrolled. Quantitative levels of HBsAg and HBV DNA were significantly correlated in 2005 (r = 0.509, p < 0.001) and 2010 (r = 0.777, p < 0.001). Concentrations of HBsAg (IU/mL) significantly decreased from 2.2 ± 1.0 log in 2005 to 1.7 ± 1.5 log in 2010 (p < 0.001). The level of HBsAg was decreased in 48 (81.4%) individuals and HBsAg was undetectable in eight (13.6%). The annual incidence of HBsAg clearance was 2.7%. These 59 HBsAg carriers in 2005 were divided into four groups: low HBsAg low HBV DNA (n = 32), high HBsAg low HBV DNA (n = 5), low HBsAg high HBV DNA (n = 12) and high HBsAg high HBV DNA (n = 10). All 32 individuals in the low HBsAg low HBV DNA group were still in that group in 2010, whereas only two of the high HBsAg high HBV DNA group became inactive. As with a younger cohort in hospital, HBsAg quantification was still well correlated with HBV DNA in elderly HBsAg carriers in the community. Lower levels of both HBsAg and HBV DNA might represent an inactive HBV infection. Copyright © 2014. Published by Elsevier Taiwan.
    The Kaohsiung journal of medical sciences 02/2015; 31(2):102-7. DOI:10.1016/j.kjms.2014.11.002 · 0.80 Impact Factor
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    ABSTRACT: Background: Hepatitis B virus (HBV) surface antigen (HBsAg) seroclearance is the ultimate serological end point in chronic hepatitis B. This study aimed to develop and validate a prediction score for spontaneous HBsAg seroclearance in HBV e antigen (HBeAg)-negative patients with chronic hepatitis B due to HBV genotype B or C. Methods: The development cohort included 2491 untreated participants from the community-based REVEAL-HBV study, who were HBeAg negative, anti-hepatitis C virus negative, and cirrhosis free. The independent validation cohort consisted of 1934 hospital-based individuals from the National Taiwan University Hospital. Clinical markers included in the model were age and serum HBV DNA and HBsAg levels. Cox proportional hazards regression models were used to create the prediction model. Results: A prediction score ranging from 0 to 27 was developed. Predicted probabilities of 5- and 10-year HBsAg seroclearance ranged from 0.95% to 30.49% and from 2.58% to 62.52%, respectively. When applied to the independent validation cohort, the areas under the receiver operating characteristic curves for the 5- and 10-year prediction of HBsAg seroclearance in the validation cohort were 0.82 (95% confidence interval [CI], .76-.88) and 0.74 (95% CI, .70-.78). Model fit was still adequate, according to Hosmer-Lemeshow goodness of fit tests. Conclusions: A clinically applicable prediction score for HBsAg seroclearance was developed and externally validated. This model can assist clinicians in further stratifying risk groups.
    The Journal of Infectious Diseases 11/2014; 211(10). DOI:10.1093/infdis/jiu659 · 6.00 Impact Factor
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    ABSTRACT: We aimed to determine whether neutrophil-to-lymphocyte ratio (NLR) could be a predictor of antiviral response in chronic hepatitis C patients. A total of 602 consecutive patients (genotype 1, n = 263; genotype 2, n = 297; others/unknown, n = 42) receiving response-guided therapy with peginterferon plus ribavirin were recruited. NLR was related to clinical and virological features and to treatment outcome. Rapid virological response (RVR) and sustained virological response (SVR) were achieved in 436 (73%) and 458 (76%) of the patients, respectively. Higher NLR (≥1.42) was found to be associated with higher prevalence of DM (P = 0.039) and higher hepatitis C viral load (P = 0.002) and white cell count (P < 0.001). NLR was significantly lower in patients with RVR and SVR compared to those without (P = 0.032 and 0.034, resp.). However, NLR was not an independent factor by multivariate analysis. In the subgroup analysis, higher NLR (≥1.42) (odds ratio, 0.494, P = 0.038) was an independent poor predictor of SVR in genotype 2 patients but was not in genotype 1 patients. In conclusion, NLR is a simple and easily accessible marker to predict response to peginterferon plus ribavirin therapy for chronic hepatitis C genotype 2.
    Disease markers 11/2014; 2014:462958. DOI:10.1155/2014/462958 · 1.56 Impact Factor
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    ABSTRACT: Polymorphisms in IFNL3 (encodes interferon λ3 or IL28B) are associated with outcomes of treatment for hepatitis C virus (HCV) infection. However, there is controversy over how polymorphisms in IFNL3 affect risk for development of hepatocellular carcinoma (HCC) in patients treated with pegylated interferon and ribavirin. In a retrospective study, we analyzed data from 1118 patients with HCV infection (589 men; median age, 60 years; 49.9% infected with genotype 1; 51.3% with advanced fibrosis) treated with pegylated interferon and ribavirin from March 2000 through October 2009 at the Chang Gung Memorial Hospital in Kaohsiung, Taiwan (71.64% achieved sustained virologic response [SVR]). Baseline samples were collected before therapy. Starting 24 weeks after treatment, clinical and biochemical features were assessed every 3-6 months and patients underwent ultrasound examinations. Lesions detected were examined by computed tomography, angiography, or fine-needle aspiration biopsy analyses. Patients were followed from the initiation of HCV therapy until diagnosis of HCC (based on published guidelines), death, or March 31, 2013 (median, 60 months). DNA samples from each patient were analyzed for rs12979860 in IFNL3. Kaplan-Meier analysis was used to determine risk for development of HCC. The percentages of patients with the IFNL3 rs12979860 CC, CT, and TT genotypes were 86.4 %, 13.2%, and 0.3%, respectively. One hundred and eight patients (9.66%) developed HCC. The IFNL3 rs12979860 CT and TT genotypes correlated with high baseline levels of α-fetoprotein (AFP; ≥20 ng/mL), advanced stage of fibrosis, diabetes, or lack of an SVR (all P<.05). Based on multivariate Cox regression analysis, age ≥60 years, low platelet count (<15×10(9) cells/L), AFP ≥20 ng/mL, advanced-stage fibrosis, diabetes, lack of an SVR, and the IFNL3 rs12979860 CT and TT genotypes were significant risk factors for HCC (P<.05). Age ≥60 years, high numbers of platelets or levels of AFP, and advanced fibrosis were risk factors for HCC among patients with SVRs. IFNL3 rs12979860 genotype did not have a significant effect on risk for HCC among patients with SVRs, although some of these patients (with the CT or TT genotype) did develop HCC. Among patients without SVRs, only fibrosis stage and the IFNL3 rs12979860 CT and TT genotypes (hazard ratio, 1.80; 95% confidence interval, 1.06-3.07; P=.030) were independent risk factors for HCC. Based on a retrospective study of patients treated for HCV infection, the IFNL3 rs12979860 CT and TT polymorphisms are associated with risk for HCC, especially in patients without SVRs. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Clinical Gastroenterology and Hepatology 11/2014; 13(5). DOI:10.1016/j.cgh.2014.10.035 · 7.90 Impact Factor
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    ABSTRACT: This study investigates the impact of general anesthesia (GA) on percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). A total of 118 treatment-naïve HCC patients in Barcelona Clinic Liver Cancer curative stage were enrolled. Patients who underwent RFA with GA were designated as the GA group, and the others were identified as the non-GA group. All the percutaneous RFA procedures were performed by the same hepatologist. The GA group comprised 42 (44.1%) patients with 71 tumors (mean size, 2.53 cm) and the non-GA group had 66 patients (55.9%) with 90 tumors (mean size, 2.35 cm). Complete tumor ablation was achieved after one session in 92.3% of the 52 GA patients, and after one to three sessions in 92.4% of 66 non-GA patients. The GA group required significantly fewer RFA sessions to obtain a similar treatment effect (p < 0.001) and the duration of hospitalization was also shortened among the GA patients (4.4 ± 0.9 days vs. 5.1 ± 1.9 days, p = 0.044). The 2-year overall survival and recurrence-free survival rates were not significantly different between the two groups. Overall, performing RFA with GA can decrease the number of sessions required to achieve complete tumor ablation in early stage HCC patients and shorten the hospitalization duration.
    The Kaohsiung journal of medical sciences 07/2014; 30(11). DOI:10.1016/j.kjms.2014.07.001 · 0.80 Impact Factor
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    ABSTRACT: Unlabelled: Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and established models for predicting HBeAg seroclearance and HBV DNA undetectability. A total of 2,139 HBsAg-seropositive, anti-HCV-seronegative, and treatment-naïve participants without liver cirrhosis at study entry were included. Spontaneous HBeAg seroclearance and HBV DNA undetectability were analyzed in 431 HBeAg-seropositive participants and 1,708 HBeAg-seronegative participants, respectively. Regression coefficients of predictors in Cox proportional hazard models were converted into integer scores for predicting seroclearance and predictive accuracy was assessed with time-dependent receiver operating characteristic (ROC) curves. The HBV DNA level was the most important predictor of HBeAg seroclearance but serum HBsAg level was the most significant predictor of HBV DNA undetectability. Compared to individuals with HBsAg levels ≥ 10,000 IU/mL, the multivariate-adjusted rate ratio (95% confidence interval) of HBV DNA undetectability was 1.20 (0.62-2.30), 2.49 (1.31-4.75), and 6.08 (3.19-11.61) for those with serum HBsAg levels of 1,000-9,999, 100-999, and <100 IU/mL, respectively. The area under the ROC curve (AUROC) of the prediction models for predicting the 5- and 10-year probabilities of HBeAg seroclearance and HBV DNA undetectability were 0.85 (0.80-0.90) and 0.78 (0.73-0.83) for HBeAg seroclearance, and 0.77 (0.72-0.82) and 0.73 (0.70-0.76) for HBV DNA undetectability. Conclusion: Prediction models incorporating important host and virus factors can predict HBeAg seroclearance and HBV DNA undetectability. Serum HBsAg levels rather than HBV DNA is the most important predictor of spontaneous HBV DNA undetectability. Serum HBsAg levels should be monitored in the management of patients with HBeAg-seronegative chronic hepatitis B.
    Hepatology 07/2014; 60(1). DOI:10.1002/hep.27083 · 11.06 Impact Factor
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    ABSTRACT: It remains unclear whether chronic hepatitis B patients who undergo interferon (IFN)-induced hepatitis B e antigen (HBeAg) seroconversion have a higher risk of hepatitis B virus (HBV) reactivation and HBeAg seroreversion than those with spontaneous HBeAg seroconversion. A total of 80 and 251 non-cirrhotic patients with interferon-induced and spontaneous HBeAg seroconversion, respectively, were analyzed. Compared to spontaneous HBeAg seroconverters, more IFN-induced HBeAg seroconverters were males (p = 0.004). For all patients, the IFN-induced HBeAg seroconverters faced a higher risk of HBV reactivation and HBeAg seroreversion than spontaneous HBeAg seroconverters (p < 0.001). For spontaneous HBeAg seroconverters, age at HBeAg seroconversion, male sex, HBV genotype C, and pre-S deletions were independent predictors of HBV reactivation. For IFN-induced HBeAg seroconverters, older age at baseline and HBV genotype C were independent predictors of HBV reactivation. To determine whether the difference in the rates of HBV reactivation or HBeAg seroreversion between two groups was age-dependent, patients were grouped and analyzed according to their age at HBeAg seroconversion (20-30, 31-39, ≥40 years). IFNs treatment was an independent factor in HBV reactivation and HBeAg seroreversion only in the groups of patients 31-39 and ≥40 years of age, but not in the group of patients 20-30 years of age. IFN-induced rather than spontaneous HBeAg seroconversion was associated with higher risk of HBV reactivation and HBeAg seroreversion, especially in patients who were older than 30 years at HBeAg seroconversion.
    Hepatology International 07/2014; 8(3):365-374. DOI:10.1007/s12072-014-9542-8 · 1.78 Impact Factor
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    ABSTRACT: Quantification of hepatitis B surface antigen (HBsAg) has been suggested to be helpful in the management of chronic hepatitis B (CHB) patients. Nucleos(t)ide analogs (NAs) are the therapy of choice for CHB and are used in the majority of CHB patients. NAs are able to induce hepatitis B virus (HBV) viral suppression, normalization of alanine aminotransferase (ALT) levels, and improvement in liver histology. Automated quantitative assays for serum HBsAg have recently become available, facilitating standardized quantification of serum HBsAg. This has led to increased interest in the clinical application of quantitative serum HBsAg for predicting therapeutic response to NAs. Recent studies have shown that a decline in serum HBsAg levels in patients receiving peginterferon may signal successful induction of immune control over HBV, and can therefore be used to predict therapeutic response. NA treatment typically induces a less rapid decline in HBsAg than interferon treatment; it has been estimated that full HBsAg clearance can require decades of NA treatment. However, a rapid HBsAg decline during NA therapy may identify patients who will show clearance of HBsAg. Currently, there is no consensus on the clinical utility of serum HBsAg monitoring for evaluating patient responses to NA therapy. This review focuses on recent findings regarding the potential application of HBsAg quantification in the management of CHB patients receiving NA therapy.
    World Journal of Gastroenterology 06/2014; 20(24):7686-7695. DOI:10.3748/wjg.v20.i24.7686 · 2.37 Impact Factor
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    ABSTRACT: Background:Obesity is considered a risk factor for hepatocellular carcinoma (HCC); The relationship between adipocytokine and HCC in hepatitis B virus (HBV) carriers remains unclear. We prospectively investigated the association of adiponectin, leptin and visfatin levels with HCC. Methods: We conducted a nested case-control study in a community-based cohort with 187 incident HCC and 374 HCC-free HBV carriers. Unconditional logistic regression was conducted to estimate the odds ratios and 95 percent confidence intervals. Results:Adiponectin, but not leptin and visfatin, levels were associated with an increased risk of HCC after adjustment for other metabolic factors and HBV related factors. The risk was increased (OR=0.51, 95% CI=0.12 - 2.11;OR=4.88 (1.46 - 16.3); OR=3.79 (1.10 - 13.0); OR=4.13 (1.13 - 15.1) with each additional quintiles, respectively) with a significant dose-response trend (ptrend =0.003). HCC risk associated with higher adiponectin level was higher in HBV carriers with ultrasonographic fatty liver, with genotype C infection, with higher viral load and with elevated alanine aminotransferase. Longitudinally, participants with higher adiponectin were less likely to achieve HBsAg seroclearance and more likely to have persistently higher HBV DNA. Eventually, they were more likely to develop liver cirrhosis (OR=1.65 (0.62 - 4.39); OR=3.85 (1.47 - 10.1); OR=2.56 (0.96 - 6.84); OR=3.76 (1.33 - 10.7) for the 2nd, 3rd, 4th and 5th quintiles, respectively; ptrend= 0.017) before HCC. Conclusions:Elevated adiponectin levels were independently associated with an increased risk of HCC. Impact: Adiponectin may play different role in the virus-induced and metabolic related liver diseases, but the underline mechanism remains unknown.
    Cancer Epidemiology Biomarkers & Prevention 06/2014; 23(8). DOI:10.1158/1055-9965.EPI-14-0161 · 4.13 Impact Factor
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    ABSTRACT: Background & Aims We compared the mortality and treatment response between lamivudine (LAM) and entecavir (ETV) in chronic hepatitis B (CHB) patients with severe acute exacerbation and hepatic decompensation. Methods From 2003 to 2010 (LAM group) and 2008 to 2010 (ETV group), 215 and 107 consecutive CHB naïve patients with severe acute exacerbation and hepatic decompensation treated with LAM and ETV respectively, were recruited. Results At baseline, LAM group had higher AST levels and end-stage liver disease (MELD) scores, and lower albumin levels than ETV group. Univariate analysis showed that LAM group had a higher rate of overall (p=0.02) and liver-related mortality (p=0.052) at week 24 than ETV group, including in patients with acute-on-chronic liver failure. Multivariate analysis showed that MELD scores, ascites, and hepatic encephalopathy were independent factors for overall and liver-related mortality at week 24. ETV or LAM treatment was not an independent factor for mortality in all patients or patients with acute-on-chronic liver failure. The best cut-off value of MELD scores were 24 for 24-week liver-related mortality. ETV group achieved better virological response (HBV DNA<300 copies/mL) than LAM group at week 24 (p=0.043) and 48 (p=0.007). T1753C/A mutation was also an independent predictor associated with overall and liver-related mortality at week 24. Conclusions The choice between ETV and LAM was not an independent factor for mortality in CHB patients with acute exacerbation and hepatic decompensation. Patients with ascites, hepatic encephalopathy, and MELD scores ⩾24 were associated with poor outcome and should be considered for liver transplantation.
    Journal of Hepatology 06/2014; 60(6). DOI:10.1016/j.jhep.2014.02.013 · 11.34 Impact Factor
  • Brian I. Carr · Chih-Yun Lin · Sheng-Nan Lu ·
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    ABSTRACT: Background Small HCCs usually arise in cirrhosis, often with associated thrombocytopenia. Many large HCC patients have normal blood platelet counts. Aims To compare parameter and phenotype patterns of patients with small <3cm and larger HCCs. Methods Retrospective analysis was undertaken of a 4139 patient HCC database to compare patient demographics, liver and tumor characteristics associated with small and large size HCCs, especially with respect to platelet counts. Results Patients with larger HCCs had more tumor nodules and PVT positivity, and had higher blood AFP, bilirubin and platelet counts. In patients with larger tumors and normal platelets (43.7% of the cohort), tumors were larger and AFP levels were higher, with lower bilirubin and AST levels than in patients with larger tumors and thrombocytopenia (17.5%). A parsimonious multinomial regression model showed high Odds Ratio for AFP and platelets for tumors >3cm with PVT. Conclusions Platelet levels are associated with distinct large HCC phenotypes.
    Seminars in Oncology 06/2014; 41(3). DOI:10.1053/j.seminoncol.2014.04.001 · 3.90 Impact Factor
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    ABSTRACT: Background/aims: Biological and epidemiological data suggest that vitamin D levels may influence cancer development. Several single nucleotide polymorphisms have been described in the vitamin D receptor (VDR) gene in association with cancer risk. We aimed to investigate the association of VDR gene polymorphisms with hepatocellular carcinoma (HCC) development in chronic hepatitis C patients. Methods: In a cross-sectional, hospital-based setting, 340 patients (201 chronic hepatitis, 47 cirrhosis and 92 HCC) and 100 healthy controls receiving VDR genotyping (bat-haplotype: BsmI rs1544410 C, ApaI rs7975232 C and TaqI rs731236 A) were enrolled. Results: Patients with HCC had a higher frequency of ApaI CC genotype (P = 0.027) and bAt[CCA]-haplotype (P = 0.037) as compared to control subjects. There were no differences in BsmI and TaqI polymorphisms between two groups. In patients with chronic hepatitis C, HCC subjects had a higher frequency of ApaI CC genotype and bAt[CCA]-haplotype than those with chronic hepatitis (P = 0.001 and 0.002, respectively) and cirrhosis (P = 0.019 and 0.026, respectively). After adjusting age and sex, logistic regression analysis showed that ApaI CC genotype (odds ratio: 3.02, 95% confident interval: 1.65-5.51) was independently associated with HCC development. Conclusion: VDR ApaI polymorphism plays a role in the development of HCC among chronic hepatitis C patients. Further explorations of this finding and its implications are required.
    Translational oncology 05/2014; 7(4). DOI:10.1016/j.tranon.2014.05.001 · 2.88 Impact Factor
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    Kwong-Ming Kee · Chao-Hung Hung · Jing-Houng Wang · Sheng-Nan Lu ·
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    ABSTRACT: The prognosis is usually poor in advanced hepatocellular carcinoma (HCC). Sorafenib is approved for Child-Pugh class A patients with unresectable and advanced HCC. We report here a rare case of a patient with advanced HCC with right portal vein thrombosis (PVT) who achieved a complete response after treatment with sorafenib. This 74-year-old man was a case of non-hepatitis B and C virus-related cirrhosis. Multiphase liver computed tomography showed an 8 cm tumor with early enhance, early wash out, and right PVT at segment 8 of the right lobe. A liver tumor biopsy confirmed the diagnosis of poorly differentiated HCC. Blood tests showed Child-Pugh class A cirrhosis and an alpha-fetoprotein level of 33,058 ng/mL. Sorafenib was initiated at 800 mg/day but was eventually reduced to 400 mg every other day because of a grade 3 hand-foot skin reaction. The alpha fetoprotein (AFP) level decreased rapidly with a linear trend after treatment. After log transformation, the calculated half-life of AFP was 6.84 days. There was no more tumor arterial enhancement, and tumor size was decreased to 3.7 cm on day 42. PVT shrank gradually and localized to the right anterior branch at month 9. There was no recurrence of tumor at the end of follow-up in month 19. Typical serial changes of clinical parameters were demonstrated in this patient.
    OncoTargets and Therapy 05/2014; 7:829-34. DOI:10.2147/OTT.S61740 · 2.31 Impact Factor
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    ABSTRACT: Unlabelled: Advanced hepatocellular carcinoma (HCC) remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT) can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods: Patients with advanced HCC who were not eligible for local therapies or were refractory to sorafenib received doxorubicin (50 mg/m(2)) and cisplatin (50 mg/m(2)) infusions into the liver via the transhepatic artery. Between January 2005 and December 2011, a total of 50 patients with advanced HCC received this treatment regimen. The overall response rate (ORR) was 22% in all treated patients. In patients who received at least 2 cycles of IACT, the ORR was 36.7%, and the disease control rate was 70%. Survival rate differed significantly between patients who received only one cycle of IACT (group I) and those who received several cycles (group II). The median progression-free survival was 1.3 months and 5.8 months in groups I and II, respectively (P < 0.0001). The median overall survival was 8.3 months for all patients and was 3.1 months and 12.0 months in groups I and II, respectively (P < 0.0001). The most common toxicity was alopecia. Four patients developed grade 3 or 4 leukopenia. Worsening of liver function, nausea, and vomiting were uncommon side effects. This study demonstrated clinical efficacy and tolerable side effects of repeated IACT with doxorubicin and cisplatin in advanced HCC. Our regimen can be an alternative choice for patients with adequate liver function who do not want to receive continuous infusion of IACT.
    05/2014; 2014:160138. DOI:10.1155/2014/160138

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  • 2015
    • National Cheng Kung University
      • Department of Internal Medicine
      臺南市, Taiwan, Taiwan
  • 2006-2015
    • Chang Gung University
      • • Department of Internal Medicine
      • • College of Medicine
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2001-2015
    • Chang Gung Memorial Hospital
      • • Division of Gastroenterology and Hepatology
      • • Department of Internal Medicine
      • • Division of Hepato-Gastroenterology
      T’ai-pei, Taipei, Taiwan
  • 2011
    • Hungkuang University
      臺中市, Taiwan, Taiwan
  • 2010
    • National Taiwan University
      • Graduate Institute of Epidemiology and Preventive Medicine
      Taipei, Taipei, Taiwan
  • 2008
    • Xiamen Chang Gung Hospital
      Amoy, Fujian, China
  • 2003
    • National Defense Medical Center
      • Department of Public Health
      Taipei, Taipei, Taiwan
  • 1998
    • Sin-Lau Hospital
      臺南市, Taiwan, Taiwan
  • 1996
    • Taiwan Landseed Hospital
      P’ing-tung-chieh, Taiwan, Taiwan