Sheng-Nan Lu

Chang Gung University, Hsin-chu-hsien, Taiwan, Taiwan

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Publications (244)1145.2 Total impact

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    ABSTRACT: Background and aims: This study compared the efficacy and safety of tenofovir disoproxil fumarate (TDF) up to 3 years innucleos(t)ide analog (NA)-naïve and NA-experienced chronic hepatitis B (CHB) patients. Methods: TDF-treated NA-naïve and NA-experienced CHB patients were retrospectively analyzed. Results: After 3 years of TDF therapy, 97.7%, 71%, and 45.5%NA-naïve patients achieved a virological response, alanine aminotransferase normalization, and hepatitis B e antigen (HBeAg) seroconversion, respectively. Compared to NA-naïve patients, NA-experienced patients without drug resistance and infected with lamivudine/telbivudine-resistant mutants showed similar results. In contrast, patients previously infected with adefovir-resistant mutants and with a suboptimal entecavir response showed significantly lower rates of virological response and HBeAg loss/seroconverion than NA-naïve patients. Mean estimated glomerular filtration rate (eGFR) markedly reduced within 12 months of TDF therapy; however, it did not decrease significantly during 12-36 months of treatment. Diabetes mellitus was an independent predictor of a ≥0.5 mg/dL increase above baseline in serum creatinine level, and age, hypertension, diabetes mellitus, and baseline creatinine level were independent factors for >20% decline in eGFR from baseline. Liver stiffness measurements improved significantly, but bone mineral density did not change significantly during treatment. Hepatocellular carcinoma (HCC) incidence was low at 36 months. Age of >60 years, cirrhosis, a low baseline platelet count, and a high α-fetoprotein level at 12 months were significant predictors of HCC development. Conclusions: TDF is effective and safe for NA-naïve and NA-experienced CHB patients, and should be used cautiously in patients with comorbidities because of a renal dysfunction risk.
    No preview · Article · Jan 2016 · Journal of Gastroenterology and Hepatology
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    ABSTRACT: Background/purpose: While new direct-acting antiviral therapies for hepatitis C virus (HCV) are the standard of care, interferon-α (IFN-α) remains a standard therapy in Taiwan based on its low cost and high response rate to IFN-α-based therapy. IFN-α exerts antiviral activity by inducing the expression of hundreds of genes that establish an antiviral state via Jak kinase (JAK)/signal transducers and activators of transcription (STAT) signaling. We quantified the transcript levels of JAK/STAT signaling genes in peripheral blood mononuclear cells of HCV genotype 1 patients and estimated the correlation between transcript levels and patient responses to IFN-α-based therapy. Methods: A total of 100 HCV genotype 1 naïve patients were enrolled. All patients received response-guided therapy for 24-48 weeks with pegylated IFN-α and ribavirin. Peripheral blood mononuclear cells were collected before treatment. Twenty patients with sustained virological responses (SVR) and 20 patients without SVR were selected for a JAK/STAT signaling genes transcript analysis using multiplex reverse transcription-polymerase chain reaction. Transcripts that were upregulated or downregulated were further validated in 100 patients. Results: Suppressor of cytokine signaling 1 (SOCS1) expression was upregulated in SVR patients compared with non-SVR patients (relative quantification = 2.14) based on a multiplex reverse transcription-polymerase chain reaction analysis. We further analyzed SOCS1 expression in 100 patients. We found that SOCS1 expression did not differ significantly between SVR and non-SVR patients. Conclusion: Peripheral blood SOCS1 expression before treatment was not associated with SVR in HCV genotype 1 patients treated with pegylated IFN-α and ribavirin.
    Preview · Article · Jan 2016 · Journal of the Formosan Medical Association
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    ABSTRACT: Background For patients with hepatocellular carcinoma (HCC), gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) improved the diagnosis, migrated Barcelona Clinic Liver Cancer (BCLC) stage, and changed therapeutic decision in retrospective analysis. Aim This prospective study was to evaluate the clinical impact of EOB-MRI on HCC management. Methods From September 2012 to February 2014, consecutive patients with suspicion of HCC in BCLC early stage by multidetector computed tomography or dynamic MRI with non-specific gadolinium, well liver function reserve, and admitted for resection evaluation were enrolled prospectively. Additional EOB-MRI was performed. The HCC diagnosis, BCLC staging, and treatment decision were obtained in a liver cancer conference. EOB-MRI impact on HCC management was analyzed. Results One hundred and three patients including 68 with typical and 35 with atypical HCC nodules in dynamic imaging studies were enrolled. EOB-MRI characterized 3 (4.4 %) benign and 33 (94.3 %) HCC for patients with typical and atypical HCC nodules, respectively. For 90 HCC patients, additional EOB-MRI changed BCLC stage in 25 (27.8 %) and treatment decision in 17 (18.9 %) patients. There were 66 patients with 78 resected nodules including 65 HCCs, 4 intrahepatic cholangiocarcinomas, and 9 benign nodules. Dynamic study and EOB-MRI detected and characterized 69 and 77 nodules, respectively. The sensitivity and accuracy in HCC diagnosis were 98.5 and 85.7 % for EOB-MRI, which were better than those of dynamic study (p < 0.001). Conclusions Additional EOB-MRI improved HCC diagnosis in sensitivity, accuracy but not specificity. It changed BCLC staging and treatment decision in 27.8 and 18.9 % of early-stage HCC patients.
    No preview · Article · Dec 2015 · Digestive Diseases and Sciences
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    ABSTRACT: Background & aims: Current hepatocellular carcinoma (HCC) staging systems only use baseline characteristics to predict outcome. We aimed to explore modifiable factors of the prognosis in HCC cases had undergone non-surgical treatment. Methods: All HCC cases in Kaohsiung Chang Gung Memorial hospital in southern Taiwan from 2002 to 2012 must met all below criteria: (1) met international diagnostic guidelines, (2) underwent the initial treatments in our hospital (3) treated by non-surgical treatment modalities and (4) survived more than two years, with follow-up time longer than five years. Results: A total 698 patients were enrolled: 451 (24.6%, group A) survivied between 2 to 5 years, and 247 (13.5%, group B) had survived > 5 years. Aside from liver function reserve and BCLC stages, four interventional factors: initial treatment modality, outcomes of 1st or 2nd treatment, and anti-viral therapy to chronic viral hepatitis were associated with prognosis. After propensity score matching, multiple logistic regression of 223 well-matched pairs showed that recurrence within one year after 1st treatment (OR: 2.17, 95% CI: 1.35-3.48), incomplete 2nd treatment (2.01, 1.27-3.17) and absence of anti-viral agents (1.68, 1.09-2.59) were independent poor prognostic factors. Conclusion: Complete treatment and anti-viral agents to chronic hepatitis were both independent modifiable prognostic factors of HCC patients had undergone non-surgical treatment. Based on these findings, timely treatment to achieve maximal locoregional control and anti-viral treatment should be provided as possible.
    Preview · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: Objective: The sodium taurocholate co-transporting polypeptide (NTCP), encoded by SLC10A1, was recently identified as a receptor for HBV. We assessed the association of the p.Ser267Phe variant (rs2296651) with chronic hepatitis B (CHB) serostatus, cirrhosis and hepatocellular carcinoma (HCC) in patients with CHB. Design: The variant was genotyped in 3801 patients with CHB and 3801 matched hepatitis B surface antigen (HBsAg) seronegative individuals. ORs with 95% CIs for the variant's association with CHB, cirrhosis and HCC were estimated using logistic regression. Results: In patients with CHB, the S267F variant was observed in 515 (18.5%) controls, 40 (17.2%) cirrhosis only cases, 49 (13.2%) non-cirrhotic HCC cases, and 52 (12.7%) cirrhotic-HCC cases. After adjustment for known risk factors, S267F was significantly associated with decreased risk for cirrhosis (OR 0.65 (95% CI 0.49 to 0.86), p=0.002) and HCC (OR 0.55 (95% CI 0.42 to 0.72), p<0.001). This association persisted for non-cirrhotic and cirrhotic-HCC. Compared with patients with HBV DNA levels greater than 10(5) copies/mL who carried the GG genotype, patients who had undetectable HBV DNA and the GA or AA genotypes had a 25-fold decreased risk of developing HCC (OR 0.04 (95% CI 0.02 to 0.11), p<0.001). The AA genotype was also associated with HBsAg seronegativity (OR 0.13 (95% CI 0.05 to 0.34), p<0.001). Conclusions: The SLC10A1 (NTCP) S267F variant is independently associated with decreased risk of cirrhosis and HCC, and resistance to CHB infection. Together with serum HBV DNA levels, S267F may help to identify patients with CHB with very low risk of HCC.
    Full-text · Article · Dec 2015 · Gut
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    ABSTRACT: Background/purpose: Recent studies have shown that serum vitamin D deficiency is a negative predictor of response to peginterferon plus ribavirin therapy for Caucasian patients with chronic hepatitis C (CHC). Whether vitamin D receptor (VDR) gene polymorphisms associate with antiviral response in Asian CHC patients remains unclear. Methods: We recruited 139 Asian patients with CHC genotype-1 who achieved 80/80/80 adherence of response-guided peginterferon plus ribavirin therapy. BsmI rs1544410, ApaI rs7975232, and TaqI rs731236 were genotyped and related to clinical and virological features and to treatment outcome. Results: Patients carrying bAt [CCA] haplotype (p=0.033), ApaI CC genotype (p = 0.033), and TaqI AA genotype (p = 0.037) had a higher HCV load as compared to those with other haplotypes, ApaI CA/AA genotype and TaqI AG genotype, respectively. A sustained virological response (SVR) was achieved in 74 (53%) of the patients. Polymorphisms in VDR gene did not correlate with rapid virological response and SVR achievement. Stepwise logistic regression analysis showed that rs12979860 CC type [odds ratio (OR): 5.56, p=0.007], platelet counts ≥ 15 × 10(10)/L (OR: 4.80, p=0.001), and rapid virological response achievement (OR: 8.36, p<0.001) were independent factors of SVR. Conclusion: Despite their associations with high hepatitis C virus load, VDR gene polymorphisms are not related to the response to peginterferon plus ribavirin therapy in Asian CHC patients.
    Preview · Article · Dec 2015 · Journal of the Formosan Medical Association
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    ABSTRACT: The aims of this study were to investigate associations between single nucleotide polymorphisms (SNPs) near the genes IFNL2, IFNL3, and IFNL4 and spontaneous clearance of hepatitis C virus (HCV) and to evaluate variants for their risk of hepatocellular carcinoma (HCC) among subjects in whom spontaneous HCV RNA clearance did not occur. In the first study, 889 untreated anti-HCV-seropositive patients without HCC symptoms were followed from 1991 to 2005. The spontaneous HCV clearance rate was found to be 33.1%. The TT variant of rs8099917 near IFNL3 was associated with increased spontaneous HCV RNA clearance, with an adjusted odds ratio (95% CI) of 2.78 (1.43–5.39), as was the newly-identified TT/TT dinucleotide variant rs368234815 near IFNL4 (adjusted odds ratio 2.68, 95% CI: 1.42–5.05). In the second study, associations between SNPs and HCC risk were examined in 483 HCC cases with detectable HCV RNA and 516 controls. In participants with HCV genotype 1, unfavorable genotypes for HCV clearance near IFNL3were associated with increased HCC risk, the adjusted odds ratio (95% CI) for rs12979860 and rs8099917 being 1.73 (1.00–2.99) and 1.84 (1.02–3.33), respectively. Host characteristics should be considered to identify high-risk patients to prioritize the use of new antiviral agents and intensive screening.
    Preview · Article · Nov 2015 · Scientific Reports
  • Shin-Yu Lu · Chi-Yu Tsai · Sheng-Nan Lu · Liang-Ho Lin
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    ABSTRACT: Background/purpose: 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. Materials and methods: A total of 60 patients on warfarin with INR <4.0 who underwent 207 dental extractions in 70 occasions were divided into two groups. Thirty-two patients were allocated to the control group (warfarin stopped and switched to heparin under hospitalization) with average preoperative INR (range) from 2.30 (1.32-3.12) brought down to 1.14 (1.04-1.32), and 28 patients were allocated to the study group (warfarin continued) with an average preoperative INR of 1.95 (1.06-3.08). Results: The incidence of postoperative bleeding in the study group was higher (3/33, 9.1%) than in the control group (3/37, 8.1%), but this difference was not significant. Local hemostasis with Gelfoam sponge was sufficient in most patients. Postoperative hemorrhage can be successfully managed by repacking with Gelfoam impregnated with tranexamic acid powder in five patients and resuturing in one patient. Conclusion: The study proved that dental extractions can be performed without interruption or alteration of warfarin regime in Taiwanese patients, provided the INR is below 4.0. A sufficient hemostasis can be obtained using local measures. This approach can save these individuals from becoming exposed to the risk of thromboembolism and the inconvenience of bridging anticoagulation with heparin.
    No preview · Article · Jul 2015 · Journal of dental sciences
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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.
    No preview · Article · Jun 2015 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association
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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.
    No preview · Article · Jun 2015 · Clinical Microbiology and Infection
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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.
    Preview · Article · May 2015 · PLoS ONE
  • Yuan-Hung Kuo · Sheng-Nan Lu

    No preview · Article · May 2015 · The Kaohsiung journal of medical sciences
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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.
    No preview · Article · Mar 2015 · Antimicrobial Agents and Chemotherapy
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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.
    No preview · Article · Feb 2015 · The Kaohsiung journal of medical sciences
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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.
    Full-text · Article · Nov 2014 · The Journal of Infectious Diseases
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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.
    Full-text · Article · Nov 2014 · Disease markers
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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.
    No preview · Article · Nov 2014 · Clinical Gastroenterology and Hepatology
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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.
    No preview · Article · Jul 2014 · The Kaohsiung journal of medical sciences
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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.
    No preview · Article · Jul 2014 · Hepatology
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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.
    No preview · Article · Jul 2014 · Hepatology International

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8k Citations
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Institutions

  • 2005-2015
    • Chang Gung University
      • • Department of Internal Medicine
      • • College of Medicine
      • • School of Medicine
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2001-2015
    • Chang Gung Memorial Hospital
      • • Division of Hepato-Gastroenterology
      • • Division of Gastroenterology and Hepatology
      • • Department of Internal Medicine
      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