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Shi-Ming Lin

Publications and source records attributed to Shi-Ming Lin.

17 recordsLinked to original sources
PubMed2006

Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: The long-term outcomes of interferon-alpha (IFN-alpha) therapy in hepatitis B e antigen (HBeAg) seropositive patients remain controversial. This study was conducted to address this issue. METHODS: The long-term outcomes were compared in 233 IFN-treated patients and 233 well-matched untreated controls. RESULTS: The cumulative incidence at the end of 15 years of follow-up (median 6.8 years, range 1.1-16.5 years) in the IFN-treated patients and controls was: HBeAg seroconversion 74.6% vs. 51.7% (P=0.031); hepatitis B surface antigen (HBsAg) seroclearance 3% vs. 0.4% (P=0.03); cirrhosis 17.8% vs. 33.7% (P=0.041); and hepatocellular carcinoma (HCC) 2.7% vs. 12.5% (P=0.011). Significant reduction of HCC was only observed in patients with pre-existing cirrhosis (P<0.01). Compared with untreated controls with persistent HBeAg, HBeAg seroconverters in untreated and IFN-treated group showed significantly lower incidence of cirrhosis and HCC (P=0.003-0.031), while non-seroconverters of IFN-treated group had marginally significant lower incidence of cirrhosis (P=0.065). Multivariate analysis showed that IFN therapy, HBeAg seroconversion and genotype B HBV infection are independent factors for better long-term outcomes. CONCLUSIONS: IFN therapy reduces cirrhosis and HCC development.

Adult↗
PubMed2006

A miniaturized germanium-doped silicon dioxide-based surface plasmon resonance waveguide sensor for immunoassay detection.

A surface plasmon resonance (SPR) waveguide immunosensor fabricated by germanium-doped silicon dioxide was investigated in this study. The designed waveguide sensor consisted of a 10 microm SiO(2) substrate layer (n=1.469), a 10 microm Ge-SiO(2) channel guide (n=1.492) and a 50 nm gold film layer for immobilization of biomolecules and SPR signal detection. The resultant spectral signal was measured by a portable spectrophotometer, where the sensor was aligned by a custom-designed micro-positioner. The results of the glycerol calibration standards showed that the resonance wavelength shifted from 628 to 758 nm due to changes of refractive index from 1.36 to 1.418. Flow-through immunoassay on waveguide sensors also showed the interactions of protein A, monoclonal antibody (mAb ALV-J) and avian leucosis virus (ALVs) resulted in wavelength shifting of 4.17, 3.03 and 2.18 nm, respectively. The SPR dynamic interaction could also be demonstrated successfully in 4 min as the sensor was integrated with a lateral flow nitrocellulose strip. These results suggest that SPR detection could be carried out on designed waveguide sensor, and the integration of nitrocellulose strip for sample filtering and fluid carrier would facilitate applications in point-of-care portable system.

Biosensing Techniques↗
PubMed2006

A novel ex vivo assay of interferon-based suppression, to predict the outcome of antiviral therapy for hepatitis C.

An ex vivo liver slice-culture method was used to develop a novel assay of pretherapy interferon-based suppression. To evaluate its clinical application, 45 consecutive patients with chronic hepatitis C were included. They underwent the ex vivo antiviral assay, followed by a 24-week course of therapy with peginterferon and ribavirin. A stepwise logistic regression model was used to estimate the relationship between sustained virological response and the presence of various clinicopathological parameters. The results indicated that the presence of an interferon-based suppression effect in the ex vivo assay (odds ratio [OR], 12.454 [95% confidence interval {CI}, 1.115-139.090]; P=.0405), clinically diagnosed liver cirrhosis (OR, 0.081 [95% CI, 0.011-0.584]; P=.0126), and the portal-inflammation score (OR, 4.220 [95% CI, 1.264-14.085]; P=.0192) were independent determinants of sustained virological response. In conclusion, this new assay serves as an independent predictor of sustained virological response in interferon-based antiviral therapy.

Antiviral Agents↗
PubMed2006

A simple noninvasive index for predicting long-term outcome of chronic hepatitis C after interferon-based therapy.

Changes in hepatic fibrosis after interferon-based therapy may be important in determining the long-term outcome of chronic hepatitis C (CHC). The use of liver biopsy for posttreatment assessment is not a viable option as a routine follow-up procedure. This study evaluated the predictive value of a simple noninvasive index, the aspartate aminotransferase (AST)-to-platelet ratio index assessed 6 months after end of treatment (APRI-M6). We evaluated APRI-M6, platelet-M6, AST-M6, and alpha-fetoprotein-M6 of 776 CHC patients with interferon-based therapy as well as the parameters at baseline of 562 untreated patients who were evaluated to predict the risk of hepatocellular carcinoma (HCC) and mortality, during a mean follow-up period of 4.75 (1.0-12.2) and 5.15 (1.0-16) years, respectively. Based on analysis of receiver operating characteristics (ROC) and using optimized cutoff point, the APRI-M6 and platelet-M6 had superior prediction models for long-term outcome with area under the curve of 0.870-0.875 and 0.824-0.847, respectively, and accuracy of 78%-81% and 76%-78%, respectively, for interferon-based-treated patients. The predictive values of all 4 parameters were poor in untreated patients. In subgroup analysis, the APRI-M6 provided a more consistent prediction ratio than platelet-M6 for sustained responders and cirrhosis-free subgroups; both parameters had similar prediction power for nonresponders and were unsatisfactory in patients with cirrhosis. According to Cox proportional hazards analysis, cirrhosis and APRI-M6 were the 2 most important factors for predicting HCC. In conclusion, APRI-M6 can accurately predict the long-term outcome of patients subjected to interferon-based treatment. Nevertheless, the data needs further validation, particularly since the predictive accuracy for patients with cirrhosis is low.

Antiviral Agents↗
PubMed2006

Emergence and takeover of precore-stop mutant prior to exacerbation of e antigen-negative chronic hepatitis B after withdrawal of lamivudine therapy.

Although hepatitis B virus (HBV) precore-stop mutant (nonsense mutation at codon 28) is usually isolated from patients with hepatitis B e antigen (HBeAg)-negative hepatitis, it is unclear whether the mutant is the cause of the hepatitis flare or it is a consequence of necroinflammation. Using the amplification-created restriction site method, the ratios of precore-stop mutant were measured in serial serum samples obtained from three patients experiencing HBeAg-negative hepatitis after withdrawal of lamivudine therapy. In all three patients, the precore-stop mutant emerged and took over the viral population at least 2 months prior to the hepatitis exacerbations. After the onset of exacerbation, transient elevation of serum HBV-DNA was observed, which was followed by progressive decrease of the ratio of precore-stop mutant as well as normalization of serum transaminases. The present data indicate that at least in some patients, the precore-stop mutant is the cause but not the consequence of the flare of HBeAg-negative hepatitis.

Adult↗
PubMed2005

Association of cytokine and DNA repair gene polymorphisms with hepatitis B-related hepatocellular carcinoma.

BACKGROUND: Hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) mainly by causing chronic necroinflammatory hepatic disease. We investigated the mechanisms underlying the inflammatory hepatocarcinogenesis by examining whether genetic variations in cytokines, antioxidant enzymes, and DNA repair genes affect the HCC risk. METHODS: We analyzed 10 polymorphisms in the genes for interleukin-1beta (IL-1B), interleukin-1-receptor antagonist (IL-1RN), tumor necrosis factor-alpha (TNF-A), glutathione S-transferase, XRCC1, hMLH1, and XPD in 577 HBV carriers with HCC and 389 HBV carrier controls. RESULTS: Overall, only the hMLH1-93*A allele significantly increased HCC risk. We identified polymorphism combinations associated with HCC. In the presence of the IL-1RN*2 allele, adjusted odds ratios (ORs) for HCC associated with C/C, T/C, and T/T genotypes of the IL-1B-31 polymorphism were 1.00, 2.93 [95% confidence interval (95% CI) 1.07-8.07], and 5.76 (95% CI 1.79-18.53), respectively. There was a dose-dependent association between the number of putative high-risk genotypes in the IL-1B, TNF-A, hMLH1, and XRCC1 genes and HCC. The adjusted OR for HBV carriers with > or = 3 putative high-risk genotypes was 9.29 (95% CI 2.90-29.75) compared with those with none or only one of the high-risk genotypes. These associations were not observed among HBV carriers without the IL-1RN*2 allele. Smoking modified the combined effect of multiple loci in the IL-1RN, IL-1B, TNF-A, hMLH1, and XRCC1 genes; a high-risk multilocus genotype only significantly increased the risk in smokers (adjusted OR 4.84; 95% CI 1.69-13.92). CONCLUSIONS: Genetic variations in cytokine and DNA repair genes contribute to susceptibility to HBV-related HCC. Smoking increased such genetic susceptibility.

Adult↗
PubMed2005

The RssAB two-component signal transduction system in Serratia marcescens regulates swarming motility and cell envelope architecture in response to exogenous saturated fatty acids.

Serratia marcescens swarms at 30 degrees C but not at 37 degrees C on a nutrient-rich (LB) agar surface. Mini-Tn5 mutagenesis of S. marcescens CH-1 yielded a mutant (WC100) that swarms not only vigorously at 37 degrees C but also earlier and faster than the parent strain swarms at 30 degrees C. Analysis of this mutant revealed that the transposon was inserted into a gene (rssA) predicted to encode a bacterial two-component signal transduction sensor kinase, upstream of which a potential response regulator gene (rssB) was located. rssA and rssB insertion-deletion mutants were constructed through homologous recombination, and the two mutants exhibited similar swarming phenotypes on LB swarming agar, in which swarming not only occurred at 37 degrees C but also initiated at a lower cell density, on a surface with a higher agar concentration, and more rapidly than the swarming of the parent strain at 30 degrees C. Both mutants also exhibited increased hemolysin activity and altered cell surface topologies compared with the parent CH-1 strain. Temperature and certain saturated fatty acids (SFAs) were found to negatively regulate S. marcescens swarming via the action of RssA-RssB. Analysis of the fatty acid profiles of the parent and the rssA and rssB mutants grown at 30 degrees C or 37 degrees C and under different nutrition conditions revealed a relationship between cellular fatty acid composition and swarming phenotypes. The cellular fatty acid profile was also observed to be affected by RssA and RssB. SFA-dependent inhibition of swarming was also observed in Proteus mirabilis, suggesting that either SFAs per se or the modulation of cellular fatty acid composition and hence homeostasis of membrane fluidity may be a conserved mechanism for regulating swarming motility in gram-negative bacteria.

Bacterial Proteins↗
PubMed2004

Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence after ablation therapy for primary tumors is common. METHODS: To evaluate the effectiveness of interferon-alpha (IFN-alpha) in preventing HCC recurrence, 30 eligible patients were randomized into three groups: 11 patients treated with three mega units (MU) of IFN-alpha three times weekly for 24 months (IFN-alpha-continuous group), 9 patients treated with 3 MU of IFN-alpha daily for 10 days every month for 6 months followed by 3 MU of IFN-alpha daily for 10 days every 3 months for a further 18 months (IFN-alpha-intermittent group), and 10 patients who received no IFN-alpha therapy (control group). The three groups were comparable in terms of etiology, demographics, and laboratory data at entry and HCC characteristics. RESULTS: After a median follow-up of 27 months (range 4-53 months), 9 patients (90%) in the control group and 9 patients (45%) in 2 treatment groups (6 patients in the IFN-alpha-continuous group and 3 patients in the IFN-alpha-intermittent group) developed an HCC recurrence (P = 0.021). Cumulative HCC recurrence rates in the IFN-alpha-intermittent, IFN-alpha-continuous, and control groups were 22.2%, 27.3%, and 40% at the end of 1 year and 33.3%, 54.6%, and 90% at the end of 4 years (P = 0.0375), respectively (control vs. IFN-alpha-intermittent group, P = 0.0123; vs. IFN-alpha-continuous group, P = 0.0822). If both IFN-alpha groups were combined, the cumulative HCC recurrence rate of the patients treated with IFN-alpha and the control group was 25% and 40% at the end of 1 year and 47% and 90% at the end of 4 years, respectively (P = 0.0135). CONCLUSIONS: The data suggested that IFN-alpha therapy may reduce HCC recurrence after medical ablation therapy for primary tumors.

Aged↗
PubMed2004

Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or =4 cm.

BACKGROUND & AIMS: The aim of this study was to compare the clinical outcome of percutaneous radiofrequency (RF) ablation, conventional percutaneous ethanol injection (PEI), and higher-dose PEI in treating hepatocellular carcinoma (HCC) 4 cm or less. METHODS: A total of 157 patients with 186 HCCs 4 cm or less were randomly assigned to 3 groups (52 patients in the conventional PEI group, 53 in the higher-dose PEI group, and 52 in the RF group). Clinical outcomes in terms of complete tumor necrosis, overall survival, local tumor progression, additional new tumors, and cancer-free survival were compared across 3 groups. RESULTS: The rate of complete tumor necrosis was 88% in the conventional PEI group, 92% in the higher-dose PEI group, and 96% in the RF group. Significantly fewer sessions were required to achieve complete tumor necrosis in the RF group than in the other 2 groups (P < .01). The local tumor progression rate was lowest in the RF group (vs the conventional PEI group, P = .012; vs the higher-dose PEI group, P = .037). The overall survival rate was highest in the RF group (vs the conventional PEI group, P = .014; vs the higher-dose PEI group, P = .023). The cancer-free survival rate was highest in the RF group (vs the conventional PEI group, P = .019; vs the higher-dose PEI group, P = .024). Multivariate analysis determined that tumor size, tumor differentiation, and the method of treatment (RF vs both methods of PEI) were significant factors in relation to local tumor progression, overall survival, and cancer-free survival. CONCLUSIONS: The results show that RF ablation yielded better clinical outcomes than conventional and higher-dose PEI in treating HCC 4 cm or less.

Aged↗
PubMed2003

Polymorphisms in XRCC1 and glutathione S-transferase genes and hepatitis B-related hepatocellular carcinoma.

Chronic infection with hepatitis B virus (HBV) causes DNA damage. An arginine (Arg)-to-glutamine (Gln) polymorphism at codon 399 in the XRCC1 gene is putatively associated with DNA damage. In a case-control study of 577 HBV surface antigen carriers with hepatocellular carcinoma (HCC) and 389 HBV carrier control subjects, we investigated the association between this polymorphism and the risk of HCC and assessed whether this association varied with glutathione S-transferase (GST) status; GSTs are involved in carcinogen metabolism. All statistical tests were two-sided. The XRCC1 Gln allele was associated with a dose-dependent increased risk of early-onset HCC (<50 years) but not with the risk of late-onset HCC (P(trend) =.01). The GSTT1-null genotype alone did not affect risk, but the GSTM1-null genotype was associated with a decreased risk for early-onset HCC. Various combinations of GSTM1 and GSTT1 genotypes differentially modified the association of XRCC1 with HCC (P(interaction) =.005); e.g., for individuals with the GSTT1-null/GSTM1-present genotype, the risk of HCC was greater for those with the Gln/Gln genotype (odds ratio = 8.07, 95% confidence interval = 1.67 to 38.93) than for those with the Arg/Arg genotype. Thus, GST status appears to affect the risk of HCC associated with this XRCC1 polymorphism.

Carcinoma, Hepatocellular↗
PubMed2003

Role of reproductive factors in hepatocellular carcinoma: Impact on hepatitis B- and C-related risk.

Hepatocellular carcinoma (HCC) is more prevalent in men than in women. Estrogen may play some role in the development of HCC. We conducted a multicenter case-control study to evaluate the effects of reproductive factors on HCC risk, and to assess whether the association between each factor and HCC differs between hepatitis B surface antigen (HBsAg)-positive and -negative women, in which hepatitis C virus (HCV) is the major cause of HCC. The study included 218 women with HCC and 729 control women selected from nonbiological and first-degree female relatives of patients with HCC. The risk of HCC was inversely related to the number of full-term pregnancies (FTP) (P(trend) =.0216) and age at natural menopause (P(trend) =.0251 among women aged 45-55 without prior surgical menopause). Oophorectomy at age or=16 years), which increased HCC risk in HBsAg carriers (multivariate-adjusted OR, 6.96; 95% CI, 2.52-19.18) but posed no increased risk in noncarriers (P(interaction) =.0053). In conclusion, increased exposure to estrogen during adulthood may provide a protective effect against HCC. Nevertheless, an early menarche, which results in early estrogen exposure, does not confer protection for HBsAg carriers.

Adult↗
PubMed2003

Power rolloff during interactive radiofrequency ablation can enhance necrosis when treating hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to compare the efficacy between standard and interactive radiofrequency ablation for treatment of hepatocellular carcinoma. SUBJECTS AND METHODS: Of 97 patients with 112 nodular hepatocellular carcinomas, 59 hepatocellular carcinomas were ablated using a standard algorithm and 53 hepatocellular carcinomas, using an interactive algorithm. For the procedure using the interactive algorithm, the electrode's array was partially retracted or fully deployed depending on the change of impedance. Complete tumor necrosis was defined as the lack of enhancement on single-detector helical CT at least 4 months after the last radiofrequency ablation. RESULTS: Complete necrosis was achieved in 101 (90%) of 112 hepatocellular carcinomas, with complete necrosis being achieved more frequently in hepatocellular carcinomas undergoing interactive ablation (96%) than standard ablation (85%) (p = 0.034). Power rolloff (a clinical end point in which power decreases as impedance increases) occurred in all of the 53 hepatocellular carcinomas that underwent interactive ablation, whereas power rolloff occurred in 48 (81%) of the 59 hepatocellular carcinomas that underwent standard ablation (p = 0.00053). Complete necrosis occurred more frequently when rolloff was achieved (96%) than without rolloff (36%) (p < 0.0001). Multivariate analysis determined that power rolloff was an independent factor in achieving complete necrosis of hepatocellular carcinomas (p < 0.0001). CONCLUSION: The use of interactive radiofrequency ablation increased the frequency of power rolloff and the rate of complete necrosis in the treatment of hepatocellular carcinoma. Power rolloff was a significant determinant of whether complete necrosis was achieved in hepatocellular carcinomas treated with radiofrequency ablation.

Adolescent↗
PubMed2003

Percutaneous local ablation therapy in small hepatocellular carcinoma.

Periodic screening programs conducted in various countries, applying sonography and serum alfa-fetoprotein to patients with chronic liver disease, have identified numerous small hepatocellular carcinoma (HCC). Although surgical resection is generally preferred for curative ablation, the long-term survival rates following resection are no better than those following local ablation. Current local ablation modalities are typically easily performed, safe and repeatable procedures, and include percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), radiofrequency ablation (RFA) and microwave coagulation therapy (MCT). The mechanisms of PEI or PAI are based on the dehydration, intracellular protein damage, and thrombo-ischemic effects of absolute ethanol or acetic acid on the tumor cells. Meanwhile, the mechanisms of RFA or MCT are based on the generation of friction heat between the tissue and electric current or microwave emitted by an RF or microwave electrode into the tumor. The heat causes coagulation, followed by cellular death as soon as the temperature in the target area exceeds 60 degrees C. From previous comparative studies of these procedures, RFA may be superior to PEI, PAI or MCT owing to its larger ablation volume, fewer treatment sessions and more predictable ablation size. The rate of complete necrosis of the target tumors was approximately 90-98% by RFA, 80-95% by PEI, 90-95% by PAI and 94% by MCT. Moreover, the survival rates of these four modalities were approximately 90% at 1 year, 70% at 3 years, and 40-50% at 5 years. In tentative conclusion, RFA is the preferred local ablation therapy for most small HCC. However, PEI is a useful alternative where RFA is unavailable.

Acetic Acid↗
PubMed2002

Androgen receptor exon 1 CAG repeat length and risk of hepatocellular carcinoma in women.

The androgen receptor (AR) gene is localized on chromosome X, and shorter CAG repeats in exon 1 of the AR gene were recently suggested to increase hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk among men. To examine whether the relationship between the AR-CAG repeats and HCC was also evident among women, we conducted a case-control study in Taiwan. The number of AR-CAG repeats was determined for 238 women with HCC and 354 unrelated control subjects (comprising 188 first-degree and 166 nonbiological relatives) selected from female relatives of patients with HCC. Women harboring 2 AR alleles with more than 23 CAG repeats had an increased risk of HCC (age-adjusted odds ratio [OR], 1.82; 95% CI, 1.06-3.14), compared with women with only short alleles or a single long allele. The association between harboring 2 AR alleles containing longer CAG repeats and HCC was more striking among HBV carriers (age-adjusted OR for more than 22 repeats, 2.23; 95% CI, 1.14-4.34) and particularly prominent among HBV carriers under age 53 years (age-adjusted OR, 3.16; 95% CI, 1.13-8.82). When CAG repeats were analyzed as a continuous variable, the increase in HCC risk associated with each incremental repeat in the shorter of 2 alleles in a given genotype was statistically significant among women with a first-degree relative with HCC (age-adjusted OR, 1.18; 95% CI, 1.01-1.37). No such relationship was detected among women without the family history. In conclusion, our observations suggest that the AR-CAG alleles may contribute to HCC predisposition among women through a mechanism different from that for men.

Adolescent↗
PubMed2002

Increased risk for hepatitis B-related liver cirrhosis in relatives of patients with hepatocellular carcinoma in northern Taiwan.

BACKGROUND: There is a tendency for familial aggregation of hepatocellular carcinoma (HCC). The aims of this study were to assess the degree to which familial aggregation of hepatitis B surface antigen (HBsAg) carriers accounts for familiality of HCC in families of hepatitis B-related HCC patients, and whether HCC shares a familial predisposition with liver cirrhosis among HBsAg carriers. METHODS: A total of 671 first-degree relatives of HBsAg-positive HCC cases were recruited using abdominal ultrasonography and tests for HBsAg and serum aminotransferases. They were from 165 simplex families defined as having only one HCC case and 72 multiplex families with more than one case. In analyses of family history of HCC and cirrhosis, the data set consisted of 4,471 unrelated asymptomatic HBsAg carriers recruited in a prospective study. RESULTS: There was no significant difference in the HBsAg-positive rate among relatives between multiplex (55.7%) and simplex (48.1%) families. Sonographic evidence of liver cirrhosis was present in 14.4% of HBsAg-positive relatives from multiplex families but in only 7.8% of HBsAg-positive relatives from simplex families (multiplex versus simplex families: adjusted odds ratio [OR] = 2.29; 95% CI: 1.10-4.77). Among unrelated asymptomatic HBsAg carriers, the adjusted OR of liver cirrhosis associated with a first-degree family history of HCC was 2.80 (95% CI: 1.68-4.66). This association was stronger in HBsAg carriers <50 years. No association was seen between family history of HCC and hepatitis activity based on elevated levels of aminotransferases. CONCLUSIONS: Familial aggregation of HCC in HBsAg carriers is associated with familial clustering of liver cirrhosis.

Adult↗
PubMedDate not supplied

Cytologic changes in small hepatocellular carcinomas after radiofrequency ablation.

OBJECTIVE: To illustrate the cytologic changes in hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). STUDY DESIGN: The study included 20 patients with 23 HCC who had undergone RFA under ultrasound guidance. Baseline cytomorphology of HCC was evaluated by fine needle aspiration (FNA) in all cases. Triphasic helical computed tomography (CT) and FNA cytology were done to evaluate the efficacy of the treatment within two weeks after RFA. The cytologic specimens were stained with Riu's method (Romanowsky stain). RESULTS: A range of cytologic findings after RFA was found, including granular and amorphous debris with artefactual aggregation, degenerated cells or necrotic material, and dyshesive, degenerated cells in a necrotic background. The cytologic patterns included necrotic cells and debris in 14 tumors and fine, granular necrosis in 9. Helical CT showed no enhancement in any of the tumors after RFA. CONCLUSION: The cell patterns indicated complete necrosis in HCC after RFA.

Adult↗