Sheng-Nan Lu

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

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Publications (226)937.69 Total impact

  • [Show abstract] [Hide abstract]
    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 : WJG. 06/2014; 20(24):7686-7695.
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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.
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    ABSTRACT: 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.
    Translational oncology. 05/2014;
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    ABSTRACT: A recent study showed that chronic hepatitis B virus (HBV) carriers with nucleos(t)ide analogue (NA)-induced hepatitis B antigen (HBeAg) seroconversion occurring before the age of 30 years have a higher risk of HBV reactivation.
    Digestive Diseases and Sciences 05/2014; · 2.26 Impact Factor
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    ABSTRACT: Background & Aims We investigated whether the quantification of hepatitis surface antigen (HBsAg) could predict HBsAg loss or hepatitis B virus (HBV) relapse after stopping lamivudine treatment. Methods A total of 188 naive chronic hepatitis B patients (83 HBeAg-positive, 105 HBeAg-negative patients), who were treated with lamivudine (treatment duration: 89.3±35.9 weeks, range: 52-243 weeks) previously but stopped the treatment for at least 12 months were recruited. Results The cumulative incidence of HBsAg loss and HBV relapse at year 6 after stopping lamivudine treatment was 24% and 65.9% respectively. Cox regression analysis revealed that lower alanine aminotransferase (ALT) at baseline, lower HBsAg levels at the end of treatment, and longer treatment duration were independent predictors for HBsAg loss, and old age, male sex and higher HBsAg levels at the end of treatment were independent predictors for post-treatment HBV relapse. At the end of treatment, the HBsAg cutoff value of 300 IU/mL could predict 55.6% (5/9) HBsAg loss in HBeAg-positive patients. In HBeAg-negative patients, the HBsAg cutoff values of 120 and 200 IU/mL could predict 79.2% (19/24) HBsAg loss and 93.3% (28/30) post-treatment sustained response respectively. Further HBsAg reduction (>0.22 log IU/mL) at month 6 after stopping treatment from the end of treatment was an independent predictor for HBsAg loss after adjusting for HBsAg level at the end of treatment. Conclusions Serum HBsAg level at the end of treatment is a useful predictor to guide the timing of stopping lamivudine treatment in chronic hepatitis B patients.
    Journal of Hepatology 05/2014; · 9.86 Impact Factor
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    ABSTRACT: Background and Aims: Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and HBV DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigates the role of serum hepatitis B surface antigen (HBsAg) levels and establishes prediction models for predicting HBeAg seroclearance and HBV DNA undetectability. Methods: A total of 2139 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 1708 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 ROC curves. Results: 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 1000-9999, 100-999, and <100 IU/mL, respectively. The AUROCs of the prediction models for predicting the five- and ten-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 2014;).
    Hepatology 02/2014; · 12.00 Impact Factor
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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 01/2014; 7:829-34. · 2.07 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. 01/2014;
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    Journal of Hepatology. 01/2014; 60(4):902–903.
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    ABSTRACT: Liver stiffness measurement (LSM) using transient elastography has been proposed to assess liver fibrosis well in various liver diseases. This study was to determine the changes of LSM and its associated factors for chronic hepatitis B (CHB) patients undergoing Entecavir therapy. Consecutive CHB patients underwent Entecavir therapy with two LSMs were enrolled. Patients with aspartate transaminase (AST) and/or alanine transaminase ≧200 IU/L were excluded. The retrospective study enrolled 233 patients including 132 without cirrhosis (group 1) and 101 with cirrhosis (group 2). The mean values of initial liver stiffness were 7.9 and 16.6 kPa for patients in group 1 and group 2, respectively (p<0.001). In addition to the decline of transaminase levels, there was significant reduction of liver stiffness value in a mean interval of 52.8 and 61.9 weeks between the two LSMs for patients in group 1 and 2, respectively (p<0.001). Multivariate analysis showed that higher initial LSM value and presence of hepatitis B e-antigen were associated with a greater decline of LSM value, whereas follow-up AST≧40 IU/L with increased LSM value for group 1 patients. For group 2 patients, longer interval between the two LSMs, higher initial LSM value and AST≧40 IU/L were associated with a greater decline of LSM value, whereas presence of diabetes mellitus (DM) contributed to increased LSM value. In conclusion, CHB patients improved their LSM values after Entecavir therapy. Higher initial LSM value contributed to greater LSM reduction. However, in cirrhotic patients, DM was associated with an increased LSM value after therapy.
    PLoS ONE 01/2014; 9(3):e93160. · 3.73 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. 01/2014;
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    ABSTRACT: The influential roles of antibiotic prophylaxis on cirrhotic patients with peptic ulcer bleeding are still not well documented. The purpose of this study is to clarify these influential roles and to identify the risk factors associated with rebleeding, bacterial infection and in-hospital mortality. A cross-sectional, chart review study was conducted on 210 cirrhotic patients with acute peptic ulcer hemorrhage who underwent therapeutic endoscopic procedures. Patients were divided into group A (with prophylactic intravenous ceftriaxone, n = 74) and group B (without antibiotics, n = 136). The outcomes were length of hospital days, prevention of infection, rebleeding rate and in-hospital mortality. Our results showed that more patients suffered from rebleeding and infection in group B than group A (31.6% vs. 5.4%; p<0.001 and 25% vs. 10.8%; p = 0.014 respectively). The risk factors for rebleeding were active alcoholism, unit of blood transfusion, Rockall score, model for end-stage liver disease score and antibiotic prophylaxis. The risk factors for infection were active alcoholism, Child-Pugh C, Rockall score and antibiotic prophylaxis. Rockall score was the predictive factor for in-hospital mortality. In conclusions, antibiotic prophylaxis in cirrhotic patients after endoscopic interventions for acute peptic ulcer hemorrhage reduced infections and rebleeding rate but not in-hospital mortality. Rockall score was the predictive factor of in-hospital mortality.
    PLoS ONE 01/2014; 9(5):e96394. · 3.73 Impact Factor
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    ABSTRACT: The development of a risk assessment tool for long-term hepatocellular carcinoma risk would be helpful in identifying high-risk patients and providing information of clinical consultation. The model derivation and validation cohorts consisted of 975 and 572 anti-HCV seropositives, respectively. The model included age, alanine aminotransferase (ALT), the ratio of aspirate aminotransferase to ALT, serum HCV RNA levels and cirrhosis status and HCV genotype. Two risk prediction models were developed: one was for all-anti-HCV seropositives, and the other was for anti-HCV seropositives with detectable HCV RNA. The Cox's proportional hazards models were utilized to estimate regression coefficients of HCC risk predictors to derive risk scores. The cumulative HCC risks in the validation cohort were estimated by Kaplan-Meier methods. The area under receiver operating curve (AUROC) was used to evaluate the performance of the risk models. All predictors were significantly associated with HCC. The summary risk scores of two models derived from the derivation cohort had predictability of HCC risk in the validation cohort. The summary risk score of the two risk prediction models clearly divided the validation cohort into three groups (p<0.001). The AUROC for predicting 5-year HCC risk in the validation cohort was satisfactory for the two models, with 0.73 and 0.70, respectively. Scoring systems for predicting HCC risk of HCV-infected patients had good validity and discrimination capability, which may triage patients for alternative management strategies.
    PLoS ONE 01/2014; 9(5):e94760. · 3.73 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 01/2014; · 9.86 Impact Factor
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    ABSTRACT: 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.
    TheScientificWorldJournal. 01/2014; 2014:160138.
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    ABSTRACT: Low-dose oral interferon could exert immune-modulating effects in human. We conducted a clinical trial to investigate the efficacy of oral interferon-alpha in preventing hepatitis C relapse. Totally 169 genotype 1b chronic hepatitis C patients having achieved end-of-therapy virological clearance were randomized to receive interferon-alpha lozenge 500 IU/day (n=59), 1,500 IU/day (n=53), or placebo (n=57) for 24 weeks. Overall, no significant differences were found for the relapse rates in the 3 groups (P>0.05). However, in patients with fibroindex 1.4-1.7, relapse occurred in 1/12 (8.3%) 500 IU-group patients versus 9/21 (42.9%) patients of the other groups (P=0.05). In 158 patients receiving at least 4 weeks of oral interferon, significantly higher platelet count was found at the end of trial in the 500 IU group (P=0.003). In thrombocytopenic patients, a significantly expedited recovery of platelet count was found in the 500 IU group (P=0.002). No drug-related severe adverse events were reported. In conclusion, at 500 IU/day, oral interferon exerted a borderline suppression effect of virological relapse in chronic hepatitis C patients with mild liver fibrosis. Additionally, it significantly expedited platelet count recovery after the end of peginterferon therapy.
    Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 11/2013; · 1.63 Impact Factor
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    ABSTRACT: The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk. This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers. The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean±SD, 4.35±1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30-75-years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither. Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.
    Gut 11/2013; · 10.73 Impact Factor
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    ABSTRACT: A prominent factor in hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). Diabetes mellitus (DM), metabolic syndrome (MetS), and obesity have also been implicated in HCC development, but these associations are not observed in all HBV- and HCV-endemic areas. We attempted to clarify the role of these factors in HCC development in an HBV- and HCV-endemic area in southern Taiwan. A community-based health examination was conducted in 2004 in Tainan County. After individuals with incomplete data and those with known HCC were excluded, there were 56,231 participants who were over 40 years of age. A further 262 HCC cases were identified from the National Cancer Registration Database records from 2005 to 2007. The hepatitis B surface antigen (HBsAg) seropositivity, anti-HCV seropositivity, platelet count, serum biochemical data, blood pressure, sociodemographic information, and anthropometric measurements were analyzed. Survival analyses were used to identify the associations between these factors and HCC. For the 262 HCC cases, male gender and age greater than 65 years were risk factors. Furthermore, a high alanine aminotransferase level, chronic HBV and/or HCV infection, and liver cirrhosis were also risk factors for HCC. However, DM, MetS and obesity were not associated with HCC development in the non-HBV-/non-HCV-infected, HBV, HCV, or dual B/C groups. In this HBV- and HCV- endemic area, DM, MetS and obesity were not risk factors for developing HCC.
    The Kaohsiung journal of medical sciences 08/2013; 29(8):451-9. · 0.50 Impact Factor
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    ABSTRACT: Ultrasound (US) is recommended for hepatic steatosis screening. The purpose of this study was to determine the usefulness of US hepatic-renal echo-intensity (HR) difference in the quantitative assessment of hepatic steatosis. Consecutive patients undergoing liver biopsy were prospectively enrolled. Using US histogram technique, the mean gray level of hepatic parenchyma and right renal parenchyma at selected regions of interest were evaluated on the same day of biopsy. With steatosis assessed by histology as the reference, the diagnostic performances of HR difference in predicting the degree of steatosis was analyzed. The optimal cut-off level, diagnostic validity and post-test probability were assessed. A total of 175 patients were enrolled (M/F, 103/72; mean age, 48.6 ± 11.7). There were 64 (36.5 %), 42 (24 %), 29 (16.6 %), 12 (6.9 %) and 28 (16 %) patients with steatosis of <5, 5-9, 10-19, 20-29 and ≥30 %, respectively. Multivariate analysis showed HR difference correlated with the severity of steatosis (R (2) = 0.425, p < 0.001) with positive correlation between HR difference and the severity of steatosis (r = 0.60, p < 0.001). The diagnostic performances were 0.927, 0.890, 0.816 and 0.760 for steatosis ≥30, ≥20, ≥10 and ≥5 %, respectively. The cut-off is 7 for diagnosing steatosis ≥30 %, with a negative predictive value of 97.6 %. The cut-off is 4 in predicting steatosis ≥5 %, with a positive predictive value of 79 %. The prevalence of steatosis influenced the post-test probability. Quantitative assessment of HR difference with US histogram technique is useful in excluding moderate to severe hepatic steatosis.
    Digestive Diseases and Sciences 07/2013; · 2.26 Impact Factor
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    ABSTRACT: Background/Aims: The independent and interactive effects of hepatitis B virus (HBV) and hepatitis C virus (HCV) factors on the development of hepatocellular carcinoma (HCC) in chronic HBV/HCV dually-infected patients remain unclear. Methods: In a cross-sectional and case-controlled study, the HBV and HCV loads and genotypes and the sequences of pre-S and precore/core promoter regions were determined in 146 HCC patients and 167 chronic carriers with HBV/HCV dual infection. Results: Age (odds ratio (OR) 1.1), male sex (OR 2.3), pre-S deletion (OR 5.0), A1762T/G1764A mutant (OR 2.5), HCV genotype-1 (OR 2.4) and platelet count <15 × 10(4)/μl (OR 1.9) were independently associated with HCC by stepwise logistic regression analysis. Patients with combined HBV mutations (pre-S deletion and A1762T/G1764A mutant) and HCV genotype-1 had a 39-fold increased risk of developing HCC compared to those with A1762T/G1764A and pre-S wild-type strains and HCV genotype non-1. In the nested case-control study, patients with HCC had a higher HBV DNA level (p < 0.001), a higher frequency of pre-S deletion (p < 0.001) and A1762T/G1764A mutant (p = 0.005), a lower HCV RNA level (p = 0.012) and a higher prevalence of HCV genotype-1 (p = 0.002) than those without. Conclusions: Pre-S deletion, A1762T/G1764A mutation and HCV genotype-1 are important in hepatocarcinogenesis in chronic HBV/HCV dual infection.
    Intervirology 07/2013; · 1.89 Impact Factor

Publication Stats

4k Citations
937.69 Total Impact Points


  • 2007–2014
    • Chang Gung University
      • • Department of Internal Medicine
      • • School of Medicine
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2001–2014
    • Chang Gung Memorial Hospital
      • • Division of Hepato-Gastroenterology
      • • Division of Gastroenterology and Hepatology
      • • Department of Internal Medicine
      T’ai-pei, Taipei, Taiwan
  • 2013
    • National Yang Ming University
      • Institute of Clinical Medicine
      Taipei, Taipei, Taiwan
    • University of California, San Diego
      • Division of Gastroenterology
      San Diego, California, United States
  • 2008–2013
    • Academia Sinica
      • Genomics Research Center
      T’ai-pei, Taipei, Taiwan
  • 2002–2012
    • National Taiwan University
      • Graduate Institute of Epidemiology and Preventive Medicine
      Taipei, Taipei, Taiwan
  • 2011
    • China Medical University Hospital
      臺中市, Taiwan, Taiwan
    • Harvard University
      Cambridge, Massachusetts, United States
    • Kaohsiung Medical University
      • College of Medicine
      Kaohsiung, Kaohsiung, Taiwan
  • 2010
    • Emory University
      Atlanta, Georgia, United States
  • 2006–2010
    • National Taiwan University Hospital
      • Department of Internal Medicine
      Taipei, Taipei, Taiwan
  • 2001–2010
    • Kaohsiung Municipal Ta-Tung Hospital, Taiwan
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2009
    • Bristol-Myers Squibb
      New York City, New York, United States
  • 2003
    • National Defense Medical Center
      • Department of Public Health
      Taipei, Taipei, Taiwan