We aimed to investigate whether response-guided therapy (RGT) with peginterferon-alpha plus ribavirin by using hepatitis C virus (HCV) genotype, pretreatment HCV RNA levels, and rapid virological response (RVR, undetectable HCV RNA at... more
We aimed to investigate whether response-guided therapy (RGT) with peginterferon-alpha plus ribavirin by using hepatitis C virus (HCV) genotype, pretreatment HCV RNA levels, and rapid virological response (RVR, undetectable HCV RNA at treatment week 4) could be applied for active HCV/hepatitis B virus (HBV) dually infected patients, without compromised the treatment efficacy.A total of 203 patients, seropositive of HCV antibody, HCV RNA and HBV surface antigen (HBsAg), and seronegative for HBV e antigen for >6 months, were randomized to receive peginterferon-alpha/ribavirin by either genotype-guided therapy (GGT, n = 102: HCV genotype 1 [HCV-1], 48 weeks; HCV-2/3, 24 weeks) or RGT (n = 101: HCV-1, 48 or 24 weeks if patients with baseline VL <400,000 IU/mL and RVR; HCV-2/3, 24 or 16 weeks if patients with RVR). The primary endpoint was HCV-sustained virological response (SVR).The HCV SVR rate was comparable between the GGT (77.5%, 79/102) and RGT groups (70.3%, 71/101, P = 0.26...
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Albinterferon is a fusion of albumin and interferon-α2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon-α for the treatment of chronic hepatitis infections. This open-label, randomized,... more
Albinterferon is a fusion of albumin and interferon-α2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon-α for the treatment of chronic hepatitis infections. This open-label, randomized, active-controlled, multicenter study investigated the safety and efficacy of albinterferon in patients with chronic hepatitis B virus (HBV) infection who were e-antigen (HBeAg) positive. One hundred and forty-one patients received one of four albinterferon doses/regimens or pegylated-interferon-α2a. Primary efficacy outcomes were changes in serum HBeAg and antibody, HBV-DNA, and alanine aminotransferase. Principal safety outcomes were changes in laboratory values, pulmonary function, and adverse events. The study was prematurely terminated as phase III trials in hepatitis C infection indicated noninferior efficacy but inferior safety compared with pegylated-interferon-α2a. Here, all treatment groups had a significant reduction in HBV-DNA from baseline. Reductions in HBV-DNA were not significantly different, except the 1200 μg every 4 weeks albinterferon dose which was inferior compared with pegylated-interferon-α2a. The serum alanine aminotransferase levels decreased in all arms. The per-patient incidence of adverse events was not significantly different for albinterferon (96.4-100%) and pegylated-interferon-α2a (93.1%). Total adverse events, however, were higher for albinterferon and correlated to dose. Decreased lung function was found in all arms (∼93% of patients), and was more common in some albinterferon groups. Albinterferon doses with similar anti-HBV efficacy to pegylated-interferon-α2a had higher rates of certain adverse events, particularly changes in lung diffusion capacity (http://www.clinicaltrials.gov number NCT00964665).
Research Interests: Treatment Outcome, Medicine, Humans, Female, Male, and 12 moreYoung Adult, Clinical Sciences, GASTROENTEROLOGY AND HEPATOLOGY., Adult, Biological markers, Hepatitis B virus, Recombinant Proteins, Polyethylene Glycols, Antiviral Agents, Interferon Alpha, Alanine Transaminase, and Gastroenterology and Hepatology
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Research Interests: Multivariate Analysis, Prospective studies, Humans, Blood Glucose, Liver, and 15 moreFemale, Male, Clinical Sciences, Aged, Middle Aged, Adult, Odds ratio, Interleukins, Biological markers, Chi Square Distribution, Logistic Models, Polyethylene Glycols, Antiviral Agents, Interferon Alpha, and prediabetic state
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Research Interests: Humans, Liver Cirrhosis, Liver, Female, Male, and 15 moreHepatocellular Carcinoma, Follow-up studies, Aged, Middle Aged, Adult, Prognosis, Enzyme Linked Immunosorbent Assay, Predictive value of tests, Confidence Interval, Vascular Endothelial Growth Factor, angiopoietin, Neoplasm staging, Liver neoplasms, Medical and Health Sciences, and Endostatin
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Research Interests: Medicine, Hepatitis C, Hepatology, Hepatitis B, Humans, and 15 moreMutation, Female, Male, Coinfection, Recurrence, Clinical Sciences, Middle Aged, Adult, Hepatitis B virus, Recombinant Proteins, Polyethylene Glycols, Antiviral Agents, Interferon Alpha, Liver neoplasms, and Medical biochemistry and metabolomics
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Research Interests: Biology, Medicine, Linear models, Multivariate Analysis, Insulin Resistance, and 15 moreHumans, Female, Male, Clinical Sciences, Genotype, Adult, Gut, Recombinant Proteins, chronic hepatitis C, Logistic Models, Polyethylene Glycols, Antiviral Agents, Interferon Alpha, Hepacivirus, and Paediatrics and reproductive medicine
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Research Interests: Medicine, Insulin Resistance, Humans, Blood Glucose, Insulin, and 15 moreLiver, Female, Male, Clinical Sciences, Middle Aged, Adult, Odds ratio, Biological markers, Chi Square Distribution, Recombinant Proteins, Logistic Models, Polyethylene Glycols, Antiviral Agents, Interferon Alpha, and Hepacivirus
Hepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is achievement of HBsAg loss with a finite course of oral antiviral... more
Hepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is achievement of HBsAg loss with a finite course of oral antiviral therapy, thereby allowing discontinuation of treatment. Significantly higher rates of HBsAg loss at 72 weeks post-treatment have been demonstrated when tenofovir disoproxil fumarate (TDF) was combined with pegylated interferon (PEG-IFN) for 48 weeks compared with either monotherapy. This analysis provides follow-up data at week 120. In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus PEG-IFN for 48 weeks (group A), TDF plus PEG-IFN for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or PEG-IFN for 48 weeks (group D). Efficacy and safety at week 120 were assessed. Rates of HBsAg loss at week 120 were significantly higher in group A (10.4%) than in group...
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Although HCV infection is highly prevalent in East Asia, these patients have been underrepresented in HRQL studies. Here we assess HRQL in East Asian HCV patients treated with different anti-HCV regimens. Patients completed Short Form-36... more
Although HCV infection is highly prevalent in East Asia, these patients have been underrepresented in HRQL studies. Here we assess HRQL in East Asian HCV patients treated with different anti-HCV regimens. Patients completed Short Form-36 (SF-36) before, during and after treatment. A total of 989 HCV patients were enrolled in two phase 3 clinical trials [China: 60.2%, South Korea: 22.4%, Taiwan: 17.4%; genotype 1: 55.3%, treatment-naïve: 57.5%; cirrhosis: 14.0%]. Patients received pegylated interferon, sofosbuvir, and ribavirin (Peg-IFN+SOF+RBV; n=130, genotypes 1, 6) or SOF+RBV (n=475, all genotypes) or SOF and ledipasvir (LDV/SOF; n=384, genotype 1). The SVR-12 rates were 94.6%, 96.2%, and 99.2%, respectively (p=0.005). During treatment, Peg-IFN+SOF+RBV-treated group experienced significant declines in most HRQL scores (by the end of treatment, mean decline up to -12.0 points, all p<0.05). Patients on SOF+RBV had milder HRQL impairment (up to -5.8 points, p<0.05 for 5/8 HRQL ...
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We investigated the long-term risk of hepatocellular carcinoma (HCC) in dual-infected hepatitis B and C patients after eradication of hepatitis C virus (HCV). A total of 164 (62% male, median age, 50.5 years) hepatitis B and C... more
We investigated the long-term risk of hepatocellular carcinoma (HCC) in dual-infected hepatitis B and C patients after eradication of hepatitis C virus (HCV). A total of 164 (62% male, median age, 50.5 years) hepatitis B and C dual-infected patients who achieved HCV sustained virological response were recruited. Half the patients were HCV genotype 1 with a median viral load of 5.5 log10 IU/mL, and 22.6%had an HBV DNA level ≥ 2000 IU/mL before therapy. HCC developed in 14 patients (8.5%), with an annual incidence of 1.38% per person-year. The 3-year, 5-year, 10-year, and 15-year cumulative probabilities were 2.5%, 5.1%, 12.6%, and 22.7%, respectively. Six months after treatment, a Cox regression hazard analysis revealed platelet level (HR: 0.98, 95% CI: 0.957-0.999, = 0.038) and AFP level (HR: 1.20, 95% CI: 1.031-1.400, = 0.019) to be independent factors in HCC. A higher 10-year cumulative risk of HCC was detected in patients with 6-month post-treatment AFP levels > 5.0 ng/mL and ...
MHC class I chain-related A (MICA) genetic variants and their serum levels (sMICA) were associated with the development of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in untreated cohorts. The dynamic changes in serial... more
MHC class I chain-related A (MICA) genetic variants and their serum levels (sMICA) were associated with the development of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in untreated cohorts. The dynamic changes in serial sMICA levels and their association with HCC in the post-curative status is elusive. Single nucleotide polymorphism rs2596542 of MICA and serial sMICA levels were analyzed in chronic hepatitis C (CHC) patients with a sustained virologic response after antivirals. Forty-two patients who developed HCC and 84 age-, gender- and cirrhosis propensity score-matched non-HCC controls were compared. Serial sMICA levels were measured within 6 months before treatment initiation (pre-sMICA), 6 months after the end-of-treatment (post-sMICA) and on the last-visit before the development (or not) of HCC (last-sMICA). Cox regression analysis revealed that last-sMICA was the only predictive factor of HCC development (hazard ratio [HR]/95 % confidence intervals [CI.]: 2...
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Long-term use of tenofovir disoproxil fumarate (TDF) reduces bone mineral density (BMD). Tenofovir alafenamide (TAF), a new prodrug of tenofovir, has shown non-inferior efficacy to TDF in patients with chronic hepatitis B virus (HBV)... more
Long-term use of tenofovir disoproxil fumarate (TDF) reduces bone mineral density (BMD). Tenofovir alafenamide (TAF), a new prodrug of tenofovir, has shown non-inferior efficacy to TDF in patients with chronic hepatitis B virus (HBV) infection, with improved bone effects at 48 weeks. We performed a randomized trial to evaluate the bone safety of TAF compared with TDF over 2 years, assessing baseline risk factors for bone loss, were evaluated after 2 years of treatment. In a double-blind study, hepatitis B e antigen (HBeAg)-positive patients (n=873) and HBeAg-negative patients (n=425) were randomly assigned (2:1) to groups given TAF (25 mg, n=866) or TDF (300 mg, n=432) once daily. We assessed bone safety, including hip and spine BMD, using dual-energy X-ray absorptiometry and measured changes in serum markers of bone turnover over 96 weeks. At baseline, treatment groups were well matched. At week 96, patients receiving TAF had significantly smaller decreases in hip BMD (mean reducti...
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Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to... more
Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to hepatocytes. In 48-week results from two ongoing, double-blind, randomized phase III trials, TAF was non-inferior to TDF in efficacy with improved renal and bone safety. We report 96-week outcomes for both trials. In two international trials, patients with chronic HBV infection were randomized 2:1 to receive 25 mg TAF or 300 mg TDF in a double-blinded fashion. One study enrolled HBeAg-positive patients and the other HBeAg-negative patients. We assessed efficacy in each study, and safety in the pooled population. At week 96, the differences in the rates of viral suppression were similar in HBeAg-positive patients receiving TAF and TDF (73% vs. 75%, respectively, adjusted difference -2.2% (95% CI -8.3 to 3.9%; p = 0.47), and in HBeAg-negative patients...
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There have been reports of reactivation of hepatitis B virus (HBV) infection during treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents. We performed a prospective study of risks and outcomes of HCV... more
There have been reports of reactivation of hepatitis B virus (HBV) infection during treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents. We performed a prospective study of risks and outcomes of HCV infection treatment with ledipasvir and sofosbuvir in patients with HBV infection. We performed a phase 3b, multicenter, open-label study in Taiwan of 111 patients with HCV infection (61% HCV genotype 1, 39% HCV genotype 2 infection; 62% women, 16% with compensated cirrhosis) along with HBV infection. All but 1 were positive for the hepatitis B surface antigen (HBsAg); 1 patient who was HBsAg-positive at screening was found to be HBsAg-negative at baseline. Overall, 33% of participants had received prior treatment for HCV and 5% had previously been treated for HBV; no patient was on HBV therapy at the start of the study. All patients received a fixed-dose combination of 90 mg of the HCV NS5A inhibitor ledipasvir with 400 mg of the NS5B nucleotide analogue i...
Research Interests: Gastroenterology, Hepatitis C, Prospective studies, Hepatitis B, Humans, and 15 moreTaiwan, Female, Male, Coinfection, Clinical Sciences, Aged, Middle Aged, Adult, Time Factors, Benzimidazoles, Hepatitis B virus, Neurosciences, Antiviral Agents, Hepacivirus, and Paediatrics and reproductive medicine
MicroRNA-125b (miR-125b) has been found to regulate inflammation and acts as an oncogene in many cancers. The mechanisms of miR-125b expression during hepatitis C virus (HCV) infection remain to be clarified. The present study aims to... more
MicroRNA-125b (miR-125b) has been found to regulate inflammation and acts as an oncogene in many cancers. The mechanisms of miR-125b expression during hepatitis C virus (HCV) infection remain to be clarified. The present study aims to identify the factors that might regulate miR-125b expression in HCV infection. High expression of miR-125b was found to correlate with HCV infection in replicon cells and in sera from HCV-infected patients, whereas the miR-125b inhibitor reduced HCV gene expression. The interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway plays an inducible effect on miR-125b gene expression. STAT3 siRNA or inhibitor could reduce HCV replication. HCV replicon cells Con1 (type 1b) and Huh7/Ava5 (type 1b) were treated with 17-hydroxy-jolkinolide B (HJB) or STAT3 siRNA. Cell viability assay and Renilla Luciferase Assay were used. Fragments of the miR-125b-1 promoter were constructed for the luciferase reporter assay. PSMB8, PSMB9, miR-12...
Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus... more
Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection. We conducted two phase 3, randomized, open-label, multicenter trials. Patients with genotype 1 infection were randomly assigned in a 1:1 ratio to receive once-daily glecaprevir-pibrentasvir for either 8 or 12 weeks. Patients with genotype 3 infection were randomly assigned in a 2:1 ratio to receive 12 weeks of treatment with either glecaprevir-pibrentasvir or sofosbuvir-daclatasvir. Additional patients with genotype 3 infection were subsequently enrolled and nonrandomly assigned to receive 8 weeks of treatment with glecaprevir-pibrentasvir. The primary end point was the rate of sustained virologic response 12 weeks after the end of treatmen...
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Interferon (IFN)-based regimens cause significant impairment of health-related quality of life (HRQL). Hepatitis C virus (HCV) cure with IFN-free regimens improves HRQL. The effect of these regimens on HRQL in East Asian HCV patients is... more
Interferon (IFN)-based regimens cause significant impairment of health-related quality of life (HRQL). Hepatitis C virus (HCV) cure with IFN-free regimens improves HRQL. The effect of these regimens on HRQL in East Asian HCV patients is unclear due to lack of published evidence. To assess HRQL in East Asian HCV patients treated with an IFN-free regimen with sofosbuvir+ribavirin. Patients completed Short Form-36 (SF-36) before, during and after treatment. 686 subjects were included (China: 56.7%; S. Korea: 18.8%; Taiwan: 12.7%; genotype 2: 40.8%; genotype 1: 29.6%; genotype 3: 18.4%; genotype 6: 11.2%; cirrhosis: 13.4%; treatment-naïve: 66.5%). Patients received either pegylated-IFN, sofosbuvir, and ribavirin (IFN+SOF+RBV) for 12 weeks (n = 155, genotypes 1 and 6) or SOF+RBV for 12-24 weeks (n = 531, all genotypes). The SVR-12 rates were 95.5% and 96.0%; respectively (P = .76). Baseline HRQL scores were similar between treatment groups (all P > .05). By the end of treatment, the I...
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The impact of additional extra-hepatic primary cancer (EHPC) on the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We retrospectively analyzed the cancer registration database from a tertiary hospital in... more
The impact of additional extra-hepatic primary cancer (EHPC) on the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We retrospectively analyzed the cancer registration database from a tertiary hospital in Southern Taiwan. Patients who were diagnosed with HCC from 2008 to 2012 were enrolled. Overall survival (OS), HCC-specific survival and recurrence after curative therapy were analyzed and compared between the patients with and the patients without EHPC. EHPC was found in 121/1506 (8.0%) patients. HCC patients with EHPC were older, more likely to be classified as Child-Pugh A, less likely to have viral hepatitis B or C, more likely to be single, had early stage HCC and received curative therapy for HCC. The OS did not significantly differ between the patients with and without EHPC(p = 0.061). However, significantly higher HCC-specific survival was observed in patients with EHPC (p<0.001), and a higher rate of non-HCC mortality was demonstrated in patie...
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Hepatitis C virus (HCV) infection is associated with thrombocytopenia. Thrombocytopenia recovers after viral eradication. The current study explored the rate and factors associated with platelet (PLT) recovery, which may represent the... more
Hepatitis C virus (HCV) infection is associated with thrombocytopenia. Thrombocytopenia recovers after viral eradication. The current study explored the rate and factors associated with platelet (PLT) recovery, which may represent the degree of liver fibrosis regression. A total of 466 patients who achieved a sustained virological response (SVR) were enrolled to compare the PLT change after a mean follow-up period of 85.5months (range 12-163 months). PLT counts increased significantly after achieving SVR (from 166±55 x103 u/L to 201±61 x103 u/L, P<0.001). The median PLT count increment was 5.03x103 u/L per year. Logistic regression analysis revealed that factors associated with slow PLT count recovery were high pretreatment PLT counts (odds ratio [OR]/ 95 % confidence intervals [C.I.]: 0.992/0.989-0.996, P<0.001) and hepatitis B virus (HBV) co-infection (OR/C.I.: 0.416/0.220-0.785, P=0.007). High platelet counts were the only factor associated with slow PLT recovery in patient...
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Hepatitis C virus (HCV) prevails in patients with thalassemia. We aimed to investigate the efficacy, safety, and impact on red blood cells (RBC) transfusion demand of pegylated interferon (Peg-IFN)/ribavirin therapy in thalassemic... more
Hepatitis C virus (HCV) prevails in patients with thalassemia. We aimed to investigate the efficacy, safety, and impact on red blood cells (RBC) transfusion demand of pegylated interferon (Peg-IFN)/ribavirin therapy in thalassemic patients with HCV. This retrospective study included 18 thalassemic patients (16 with HCV-1b, one HCV-1b/2b, and one HCV-2b) and 54 consecutive sex- and genotype-matched controls. Patients with HCV-2, or HCV-1 or mixed HCV-1/2 with lower viral loads plus rapid virological response (RVR) received 24-week Peg-IFN/ribavirin; whereas HCV-1 or mixed HCV-1/2 with higher viral loads or without RVR received 48-week regimens. The rates of RVR, complete early virological response, and sustained virological response (SVR) in thalassemic patients were 72.2% (13/18), 94.1% (16/17), and 77.8% (14/18), which resembled those of controls (63.0%, 94.4%, and 81.5%, respectively). RVR was the only significant factor associated with SVR in thalassemic group, and was the strong...
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Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non-viral causes of HCC, particularly non-alcoholic fatty liver disease (NAFLD), are becoming... more
Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non-viral causes of HCC, particularly non-alcoholic fatty liver disease (NAFLD), are becoming increasingly prevalent. The aim of this study was to compare the clinical characteristics and survival of cryptogenic and viral HCC. We conducted a retrospective cohort study involving 3878 consecutive HCC patients seen at two tertiary centres in the United States and one in Taiwan from 2004 to 2014. We compared the clinical characteristics, treatment and survival of patients by underlying aetiology: cryptogenic (n = 696), HBV (n = 1304) or HCV (n = 1878). Cirrhosis was present in 66.8% of the cryptogenic HCC patients, compared with 74.7% of HBV-related HCC (HBV-HCC) (P = .001) and 85.9% of HCV-HCC (P < .001). Compared to viral HCC, cryptogenic HCC patients presented with larger tumours and at later stages of disease. Five-year overall survival was 16.3% a...
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Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting... more
Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infection. High concentration of heparin has been commonly used as an inhibitor control for in vitro infection in the field. Surprisingly, we found that heparin at physiological concentration can enhance HBV infection in a PreS1-peptide sensitive, NTCP-dependent manner in both HepaRG and HepG2-NTCP-AS cells. O-sulfation of heparin is more important for the infection enhancement than N-sulfation. This system based on the HepG2-NTCP-AS cells can support in vitro infection with HBV genotypes B and C...
The aim of this study was to ascertain the relationships of blood pressure, fasting sugar level, triglyceride (TG) level, uric acid level, and body mass index (BMI) with proteinuria and the estimated glomerular filtration rate (eGFR) in a... more
The aim of this study was to ascertain the relationships of blood pressure, fasting sugar level, triglyceride (TG) level, uric acid level, and body mass index (BMI) with proteinuria and the estimated glomerular filtration rate (eGFR) in a population from southern Taiwan. The 20,900 subjects enrolled in this study had undergone a free adult health examination under the National Health Insurance scheme between September 2005 and June 2011. Factors such as blood pressure, blood sugar, TG, uric acid and BMI were examined in terms of their relationships with the eGFR (calculated according to the Taiwanese Modification of Diet in Renal Disease (Taiwanese-MDRD)) and proteinuria. The Chi-square test, Student's t-test or the Mann-Whitney U-test, and multivariate logistic regression analysis were employed. The prevalence of chronic kidney disease (CKD) was 66.7%. Multivariate logistic analysis showed that fasting sugar (OR = 1.12 and 1.65), blood pressure (OR = 1.09 and 1.12), and triglyc...
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Treatment rates with interferon-based therapies for chronic hepatitis C have been low. Our aim was to perform a systematic review of available data to estimate the rates and barriers for antiviral therapy for chronic hepatitis C. We... more
Treatment rates with interferon-based therapies for chronic hepatitis C have been low. Our aim was to perform a systematic review of available data to estimate the rates and barriers for antiviral therapy for chronic hepatitis C. We conducted a systematic review and meta-analysis searching MEDLINE, SCOPUS through March 2016 and abstracts from recent major liver meetings for primary literature with available hepatitis C treatment rates. Random-effects models were used to estimate effect sizes and meta-regression to test for potential sources of heterogeneity. We included 39 studies with 476,443 chronic hepatitis C patients. The overall treatment rate was 25.5% (CI: 21.1-30.5%) and by region 34% for Europe, 28.3% for Asia/Pacific, and 18.7% for North America (p = 0.008). On multivariable meta-regression, practice setting (tertiary vs. population-based, p = 0.04), region (Europe vs. North America p = 0.004), and data source (clinical chart review vs. administrative database, p = 0.025)...
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Hepatocellular carcinoma (HCC) surveillance is associated with improved outcomes and long-term survival. Our goal is to evaluate adherence rates to HCC surveillance. We performed a systematic search of the PubMed and Scopus databases and... more
Hepatocellular carcinoma (HCC) surveillance is associated with improved outcomes and long-term survival. Our goal is to evaluate adherence rates to HCC surveillance. We performed a systematic search of the PubMed and Scopus databases and abstract search of relevant studies from recent major liver meetings. All searches and data extraction were performed independently by 2 authors. Analysis was via random-effects models and multivariate meta-regression. A total of 22 studies (n=19,511) met inclusion criteria (original non-interventional studies with defined cirrhosis or chronic hepatitis B or chronic hepatitis C with advanced fibrosis populations, and surveillance tests and intervals). Overall adherence rate was 52% (95% CI 38-66%). Adherence was significantly higher in cirrhotic patients compared to chronic hepatitis B and other high risk patients, in European compared to North American studies, in less than 12-month compared to yearly surveillance intervals, and in prospective comp...
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Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP) has recently been developed as a promising liver fibrosis glyco biomarker. We assessed its efficacy in evaluating liver disease severity in chronic hepatitis C... more
Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP) has recently been developed as a promising liver fibrosis glyco biomarker. We assessed its efficacy in evaluating liver disease severity in chronic hepatitis C (CHC) in Taiwan. The association between WFA(+)-M2BP and histological features was evaluated among those CHC patients underwent liver biopsy. We also aimed to clarify the factors determining the performance of WFA(+)-M2BP in CHC. A total of 229 CHC patients were consecutively recruited. The mean value of WFA(+)-M2BP in patients from F0 to F4 was 1.68, 2.23, 3.45, 3.48, 3.77 respectively (linear trend P = 0.008). Linear regression analysis revealed that alanine aminotransferase (odds ratio [OR]: 0.03, 95% confidence intervals [CI]: 0.02-0.05, P < 0.001), AST (OR: -0.1, 95% CI: -0.02 to -0.01, P < 0.001), and liver fibrosis (OR: 0.30, 95% CI: 0.01-0.59, P = 0.043) were the independent factors correlated to serum WFA(+)-M2BP level. The optimal cuto...
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The role of directly-acting antivirals (DAA)-containing regimens in the treatment of patients dually-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) remains unclear. The pilot study aimed to explore the safety and... more
The role of directly-acting antivirals (DAA)-containing regimens in the treatment of patients dually-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) remains unclear. The pilot study aimed to explore the safety and efficacy of a protease inhibitor, boceprevir, in combination with peginterferon/ribavirin for HCV genotype 1 (HCV-1)/HBV dually-infected patients refractory to prior peginterferon/ribavirin. Twelve peginterferon-experienced patients dually-infected with HCV-1/HBV were assigned to receive boceprevir 800 mg, twice a day, plus peginterferon-α 2b 1.5 μg/kg/week and ribavirin 800-1400 mg/day for 36 or 48 weeks. The primary endpoint was HCV sustained virological response (SVR, HCV RNA undetectable 24 weeks after end-of-treatment). Five patients terminated treatment early due to adverse events (one at week 4, one at week 46), virological failures (one non-response and one breakthrough), and patient request (n = 1). Eight patients achieved HCV SVR (66.7% in full-...
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This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological... more
This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004-2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22-0.63) for those without cirrhosis and 0.54 (0.31-0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased ...
Chronic hepatitis C (CHC) infection poses a global healthcare burden, being associated with serious complications if untreated. The prevalence of hepatitis C virus (HCV) infection is highest in areas of Central, South, and East Asia; over... more
Chronic hepatitis C (CHC) infection poses a global healthcare burden, being associated with serious complications if untreated. The prevalence of hepatitis C virus (HCV) infection is highest in areas of Central, South, and East Asia; over 50% of HCV patients worldwide live in the region, where HCV genotypes 1b, 2, 3, and 6 are the most prevalent. Treatment outcomes for chronic hepatitis C vary by ethnicity, and Asian patients achieve higher sustained virologic response rates following interferon (IFN)-based therapy than non-Asians. However, low efficacy, poor safety profile, and subcutaneous administration limit the use of IFN-based therapies. Superior virologic outcomes have been observed with different classes of direct-acting antivirals (DAAs) alone or in combination, and several all-oral DAA regimens are available in Asia. These regimens have shown excellent efficacy and favorable tolerability in clinical trials, yet there is a need for further studies of DAAs in a real world co...
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Genetic variants of MHC class I polypeptide-related chain A (MICA) at rs2596542 have been associated with hepatocellular carcinoma. The linkage between serum MICA (sMICA) and liver fibrosis in chronic hepatitis C is elusive. Linear... more
Genetic variants of MHC class I polypeptide-related chain A (MICA) at rs2596542 have been associated with hepatocellular carcinoma. The linkage between serum MICA (sMICA) and liver fibrosis in chronic hepatitis C is elusive. Linear regression analysis revealed that sMICA were independently correlated to α-fetoprotein (β: 0.149; 95% confidence interval [CI]: 0.001, 0.003; P = 0.007)and MICA rs2596542 GG genotype (β: 0.209; 95% CI: 0.153, 0.483; P < 0.001). While patients were stratified by MICA genetic variants, advanced fibrosis was the only factor independently correlated to sMICA among A allele carriers (β: 0.234; 95% CI: 0.107, 0.543; P = 0.004) but not among non-A allele carriers. Logistic regression analysis revealed that factors associated with advanced liver fibrosis was sMICA (OR/CI: 2.996/1.428-6.287, P = 0.004) and platelet counts (OR/CI: 0.988/0.982-0.994, P < 0.001) in MICA rs2596542 A allele carriers. sMICA > 50 pg/mL provided a positive predictive value of 72 ...
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Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of... more
Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients. A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated. We demonstrated that the average cost per SVR ach...
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Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. CHC patients receiving pan-oral DAA therapy from... more
Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. CHC patients receiving pan-oral DAA therapy from Dec. 2013 to Aug. 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen (HBsAg)) and positive hepatitis B core antibody (Anti-HBc)) and 7 patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation. The overall SVR12 rate was 96.9%, and 2 patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the 7 patients with a current HBV infection, HBV virological reactivation was found in 4 (57.1%) of the 7 ...
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Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma over time. We aimed to explore their impact at the initiation of antiviral therapy on hepatocellular carcinoma among chronic hepatitis C (CHC)... more
Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma over time. We aimed to explore their impact at the initiation of antiviral therapy on hepatocellular carcinoma among chronic hepatitis C (CHC) patients. A total of 1,281 biopsy-proven CHC patients receiving IFN-based therapy were followed for a mean period of 5.5 years. The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non-sustained virological response (SVR) and SVR patients who were <40 years old (7.7% vs. 0.5%, P = 0.1) but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%, P < 0.001) and >55 years old (15.1% vs. 7.9%, P = 0.03). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients 40 to 55 years old [HR/95% confidence intervals (CI), 10.92/3.78-31.56; P < 0.001] and >55 years old (HR/CI, 1.96/1.06-3.63; P = 0.03) but not in patients <40 years old (HR/CI, 2.7...
Colchicine is a very cheap microtubule destabilizer. Because microtubules are an ideal target for anticancer drugs, the purpose of this study was to investigate whether clinically acceptable colchicine concentrations have anticancer... more
Colchicine is a very cheap microtubule destabilizer. Because microtubules are an ideal target for anticancer drugs, the purpose of this study was to investigate whether clinically acceptable colchicine concentrations have anticancer effects on gastric cancer cells, and its possible anticancer mechanisms. Two human gastric cancer cell lines (i.e., AGS and NCI-N87) were investigated by proliferative assay, microarray, quantitative reverse transcriptase-polymerase chain reaction, and a nude mice study using clinically acceptable colchicine concentrations (2 ng/mL and 6 ng/mL for in vitro tests and 0.07 mg colchicine/kg/d for in vivo tests). Our results showed that colchicine had the same inhibitory effects on the proliferation of both cell lines. The antiproliferative effects of colchicine on both cell lines were achieved only at the concentration of 6 ng/mL (p < 0.0001). In both cell lines, 18 genes were consistently upregulated and 10 genes were consistently downregulated by 6 ng/...
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The treatment responses of sorafenib in hepatocellular carcinoma are modest which may be due to different characteristics of cancer cells or insufficient therapeutic concentrations. This study was to clarify this issue. The... more
The treatment responses of sorafenib in hepatocellular carcinoma are modest which may be due to different characteristics of cancer cells or insufficient therapeutic concentrations. This study was to clarify this issue. The anti-proliferative effects and differential expressions of 8 genes related to sorafenib anti-cancer mechanisms (tyrosine kinase receptor genes: KDR, PDGFRB; RAF cascade: RAF1, BRAF, MAP2K1, MAP2K2, MAPK1, MAPK3) were investigated in primary cultured hepatocellular carcinoma cells collected from 8 patients using clinically applied sorafenib concentrations (5, 10μg/mL). The anti-proliferative effects of sorafenib at either 5 or 10μg/mL, which were related to down-regulations of KDR, PDGFRB and/or genes in the RAF cascade, were achieved only in one patient (HCC38/KMUH). However, either 5 or 10μg/mL sorafenib promoted proliferation in 4 patients (HCC29/KMUH, HCC62/KMUH, HCC87/KMUH, HCC98/KMUH). Among them, the RAF cascade, PDGFRB and/or KDR were up-regulated in 3 pat...