Biomedical subjects

D S Chen

Publications and source records attributed to D S Chen.

At least 37 records · Page 2Linked to original sources

PubMed2001

Prolonged interferon treatment after combination interferon and ribavirin therapy in patients with chronic hepatitis C: a clinical trial of interferon relapsers and non-responders.

BACKGROUND AND PURPOSE: For the retreatment of chronic hepatitis C patients relapsing after, or non-responsive to, previous interferon therapy, the efficacy of combination therapy with interferon alfa plus ribavirin is superior to interferon alone. The aim of this study was to determine whether prolonged interferon alfa treatment after 24-week combination therapy can further increase the efficacy of combination therapy. METHODS: Nineteen interferon relapsers and 17 interferon non-responders were randomly assigned to receive either interferon alfa 5 million units (MU) thrice weekly plus oral ribavirin 1,200 mg daily for 24 weeks (regimen A) or interferon alfa 5 MU thrice weekly plus oral ribavirin 1,200 mg daily for 24 weeks followed by interferon alfa 3 MU thrice weekly for another 24 weeks (regimen B). Efficacy was assessed by normalization of serum aminotransferase concentrations and disappearance of serum hepatitis C virus (HCV) RNA at the end of treatment and at 24 weeks after stopping treatment. RESULTS: Overall, 67% of relapsers receiving regimen A and 80% of those receiving regimen B had sustained virologic responses 24 weeks after stopping treatment. In contrast, 45% of non-responders receiving regimen A and 63% of those receiving regimen B had sustained responses. The sustained response was more common in relapsers with non-1b HCV genotypes. The sustained response rate to combination therapy was 50% or more in patients with genotype 1b infection. CONCLUSIONS: Prolonged interferon treatment after combination therapy has a comparable efficacy to combination therapy alone for the retreatment of chronic hepatitis C patients relapsing after, or non-responsive to, previous interferon therapy.

Adult↗

PubMed2001

Probable reinfection with hepatitis C virus in a chronic hepatitis C patient with a sustained response to combination therapy.

Superinfection with hepatitis C virus (HCV) in already chronically infected subjects has been documented. Whether a complete response to antiviral therapy is associated with protective immunity against reinfection with HCV remains unknown. We describe a patient who had a sustained biochemical and virologic response with loss of intrahepatic HCV RNA after a course of combination therapy using interferon plus ribavirin. Histopathologically, the chronic hepatitis was in remission on follow-up biopsy 6 months post-therapy. Unfortunately, 34 weeks post-therapy, a flare of hepatitis with reappearance of hepatitis C viremia was noted 2 months after he received injections from a non-licensed medical provider. Analysis of the core gene sequences showed a 95% homology between the HCV strains isolated before antiviral treatment and during the hepatitis flare. The data indicated that the hepatitis flare after a period of sustained response to combination therapy in this patient could have been caused by reinfection with homotypic HCV. Our observation indicates the lack of protective immunity against reinfection with HCV in patients with chronic hepatitis C, even after successful clearance of the virus. Therefore, reinforcing the education of these subjects to avoid HCV reinfection should be stressed.

Antiviral Agents↗

PubMed2000

Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls.

CONTEXT: Hepatocellular carcinoma (HCC) has a male predominance and is closely related to hepatitis B virus (HBV) infection. Hepatitis B virus vaccination was launched in 1984 in Taiwan for neonates of mothers carrying hepatitis B e antigen, resulting in a decreased incidence of HCC in children. The effect on boys vs girls is not known. OBJECTIVE: To evaluate the association between a HBV vaccination program with incidence of childhood HCC by sex. DESIGN AND SETTING: Analysis of data collected from Taiwan's National Cancer Registry System and the Taiwan Childhood Hepatoma Study Group between 1981 and 1996. PARTICIPANTS: Children aged 6 to 14 years who were diagnosed as having HCC (201 boys and 70 girls). MAIN OUTCOME MEASURE: Incidence of HCC in boys and girls before and after implementation of the vaccination program. RESULTS: The boy-girl incidence ratio decreased steadily from 4.5 in 1981-1984 (before the program's introduction) to 1.9 in 1990-1996 (6-12 years after the vaccination program was launched). The incidence of HCC in boys born after 1984 was significantly reduced in comparison with those born before 1978 (relative risk [RR], 0.72; P =.002). No significant decrease in HCC incidence was observed in girls born in the same periods (RR, 0.77; P =.20). The incidence of HCC in boys remained stable with increasing age, while an increase of HCC incidence with age in girls was observed. These age and sex effects remained the same regardless of birth before or after the vaccination program. CONCLUSION: Our results suggest that boys may benefit more from HBV vaccination than girls in the prevention of HCC.

Adolescent↗

PubMed2000

Tumor-induced immunosuppression: a barrier to immunotherapy of large tumors by cytokine-secreting tumor vaccine.

An active immunotherapy strategy with cytokine-assisted tumor vaccine, although often effective for small tumor burdens, is much less so for large tumor burdens. This study examines how large tumors might suppress the T cell functions and escape from the immune responses elicited by a granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccine. According to our results, the T cells isolated from the tumor-bearing mice treated late with the vaccine failed to confer protective activity on naive mice against a wild-type tumor challenge, unlike those isolated from the early-treated group. Nevertheless, the antitumor activity of the inactive T cells could be restored on in vitro stimulation. Expression of transforming growth factor beta (TGF-beta) and interleukin 10 (IL-10), the potent immunosuppressive factors, was detected in the parental tumor cell line RLmale 1 (a murine T leukemia cell line), as well as in the tumor region, the levels of which correlated with tumor progression. An in vitro assay of T cell functions revealed that the TGF-beta in the conditioned medium of RLmale 1 cells mainly affected the activation, whereas the IL-1male affected the activation to a lesser extent, but significantly affected the cytolytic activity, of tumor-specific T cells. The immunosuppressive activity of IL-10 was also signified by the findings that administration of the conditioned medium of RLmale 1 cultured in a serum-free medium, in which the TGF-beta activity was then lost while the IL-10 activity still remained, or of recombinant IL-10 to the early-treated group of mice abrogated the known efficacy of tumor vaccine on the small tumors. These data suggested that the efficacy of cytokine-secreting tumor vaccine was blocked by the immunosuppressive factors secreted from the large tumors. The results have important implications for the clinical design of immunotherapeutic strategies for advanced cancer patients.

Animals↗

PubMed2000

TT virus infection in patients with chronic hepatitis B or C: influence on clinical, histological and virological features.

Concomitant infection with TT virus and hepatitis B virus (HBV) or hepatitis C virus (HCV) is common. However, the effect of TTV infection on chronic hepatitis B or C is unknown. The prevalence of TTV infection, the effect of TTV infection on the clinical, histological and virological features of patients with chronic hepatitis B or C, and the influence of TTV infection on the HCV response to interferon alfa therapy were studied. A total of 100 asymptomatic hepatitis B surface antigen carriers, 220 patients with HBV-related chronic liver diseases, and 110 patients with chronic hepatitis C treated with interferon alfa (3 million units subcutaneously three times a week for 24 weeks) were enrolled. Serum HCV RNA and serum TTV DNA were detected by the polymerase chain reaction (PCR). Serum HBV DNA and serum HCV RNA level were quantified by branched DNA assays. Infection with TTV was detected in 21.5% of HBV carriers and 37% of HCV carriers. TTV infection had little effect on the clinicopathological course of chronic HBV infection. In chronic hepatitis C, clinical features, histological severity, serum HCV RNA levels, and the response to interferon alfa therapy did not differ between those with and without TTV infection. The loss of serum TTV DNA did not correlate with the biochemical response as did in the loss of serum HCV RNA. In conclusion, TTV infection is found frequently in patients with chronic hepatitis B or C in Taiwan; however, coinfection with TTV does not affect the clinicopathological course of chronic hepatitis B or C and the response to interferon alfa therapy.

Adult↗

PubMed2000

Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B.

BACKGROUND & AIMS: Six genotypes (A-F) of hepatitis B virus (HBV) have been identified; however, the genotype-related differences in the pathogenicity of HBV remain unknown. Therefore, we investigated the prevalence of HBV genotypes in Taiwan and the association between distinct genotypes and severity of liver disease in a cross-sectional study. METHODS: Using a molecular method, HBV genotypes were determined in 100 asymptomatic carriers and in 170 patients with histologically verified chronic liver disease and hepatocellular carcinoma (HCC). RESULTS: All genotypes except genotype E were identified in Taiwan, and genotypes B and C were predominant. Genotype C was prevalent in patients with cirrhosis and in those with HCC who were older than 50 years compared with age-matched asymptomatic carriers (60% vs. 23%, P < 0.001, and 41% vs. 15%, P = 0.005, respectively). Genotype B was significantly more common in patients with HCC aged less than 50 years compared with age-matched asymptomatic carriers (80% vs. 52%, P = 0.03). This predominance was more marked in younger patients with HCC (90% in those aged </=35 years), most of whom did not have cirrhosis. CONCLUSIONS: Our data suggest that HBV genotype C is associated with more severe liver disease and genotype B may be associated with the development of HCC in young Taiwanese. However, additional large-scale longitudinal studies are needed to confirm the relationship of HBV genotypes to liver disease severity and clinical outcomes.

Adult↗

PubMed2000

Hepatitis B genotypes and the response to interferon therapy.

BACKGROUND/AIMS: Possible pathogenic differences among hepatitis B virus (HBV) genotypes have been observed; however, the response to interferon therapy among HBV genotypes remains unknown. We therefore analyzed the efficacy of interferon alfa in the treatment of chronic hepatitis B patients with different HBV genotypes. METHODS: Fifty-eight genotype B or C infected chronic hepatitis B patients who had been treated with interferon alfa-2b were retrospectively studied. The response to interferon was defined as normalization of serum aminotransferase level, loss of hepatitis B e antigen and HBV DNA 48 weeks post-treatment. RESULTS: Baseline data of both groups of patients were comparable; however, genotype C patients had a higher serum aminotransferase level and a higher frequency of core promoter mutation. The response rate was 41% and 15% in genotype B and C patients, respectively (p=0.045). In those with higher serum aminotransferase levels, the response rate was 50% and 17%, respectively (p=0.025). Additionally, younger age and genotype B infection may predict a better response to interferon alfa. CONCLUSIONS: HBV genotype C, compared to genotype B, is associated with a higher frequency of core promoter mutation, and a lower response rate to interferon alfa therapy.

Adult↗

PubMed2000

Ribavirin enhancement of hepatitis C virus core antigen-specific type 1 T helper cell response correlates with the increased IL-12 level.

BACKGROUNDS/AIMS: Combination IFN-a and ribavirin therapy for hepatitis C virus-infected patients has been reported to improve the response rate up to 50%. In this study, we aimed to study further the role of ribavirin in hepatitis C virus-specific immune responses. METHODS: We immunized mice with hepatitis C virus core protein with or without different concentrations of ribavirin. Forty days after immunization, hepatitis C virus-specific immune responses were followed in these mice. RESULTS: We found that the mice immunized with core antigen once every 2 weeks and 0.5 mg ribavirin every day showed higher levels of core-specific IgG2 compared with those mice immunized with core antigen only. In addition, core antigen-stimulated spleen cells produced higher levels of T helper type 1 cytokines and the core-specific cytotoxic T cell activity also increased significantly. Furthermore, lipopolysaccharide-stimulated peritoneal cells produced higher levels of IL-12 in ribavirin-treated mice, and peritoneal cells isolated from naive mice also produced significantly higher level of IL-12 when cultured with ribavirin. CONCLUSIONS: Ribavirin may significantly promote the T helper type 1 immune response in vivo, and, furthermore, the effect of ribavirin on IL-12 level produced by accessory cells may contribute to the T helper type 1 enhancing effect.

Animals↗

PubMed2000

Public health measures to control hepatitis B virus infection in the developing countries of the Asia-Pacific region.

Hepatitis B virus (HBV) infection is prevalent in the Asia-Pacific region and the disease burden caused by chronic HBV infection has been enormous. Although vaccination programmes have been implemented in the past decade, and there are extremely successful countries in the region, many countries still cannot afford a control program. These countries are often populous and highly endemic for HBV infection. To overcome this, aid from developed countries or private foundations should be actively sought. In the developing countries of this region, HBV infection in early childhood is the main cause of chronic HBV status, and thus universal vaccination of all infants is the best way to control HBV infection. Because of the expense and extra costs of screening pregnant women, the use of hepatitis B immune globulin may not be essential. To achieve the goal of universal infant vaccination, public education should be done in parallel with education of health professionals and control measures. The Asia Pacific region has more people with chronic hepatitis B than any other part of the world, and control of HBV infection in this region will no doubt be the most important and challenging task to be taken in the beginning of the new millennium.

Asia↗

PubMed2000

Transmission of hepatitis C virus in Asia: past and present perspectives.

Hepatitis C virus (HCV) infection is a major public health problem. The epidemiology of HCV infection in different parts of Asia is similar, with an average seroprevalence of hepatitis C antibody (anti-HCV) less than 2.5% in healthy adults. The infection is rarely seen in children. The major routes of HCV transmission in Asia during the past few decades have been through administration of therapeutic blood products and injecting drug use, similar to the pattern observed in other parts of the world. However, obvious parenteral routes of transmission only account for 30-60% of anti-HCV-positive cases, depending on the geographic area. Other inapparent parenteral or per-mucosal exposures, including medical intervention, tattooing, acupuncture, vertical and sexual transmission, accidental needlestick and household contact, are also possible routes of HCV transmission. Although screening of blood donors for anti-HCV and improvements in infection control have significantly decreased the exposure to HCV, it is believed that HCV is still spreading in some areas of Asia because of the lack of routine screening of donated blood, injecting drug usage, traditional medicine practices or medical treatment under suboptimal hygienic conditions that involve blood contamination, and tattooing. Accordingly, until effective and safe immunoprophylaxis is available, interruption of transmission routes, such as implementation of blood donor screening for anti-HCV, adequate sterilization of surgical instruments or the use of disposable medical instruments, especially needles and syringes, and avoidance of sharing personal grooming aids remains the mainstay to prevent HCV infection in Asia today.

Asia↗

PubMed2000

Low incidence of hepatitis C virus transmission between spouses: a prospective study.

BACKGROUND: Interspousal transmission of hepatitis C virus (HCV) has been documented; however, the annual risk of interspousal transmission remains unclear. METHODS: A long-term prospective study to define the risk of interspousal transmission of HCV was conducted. One hundred and twelve index patients with chronic hepatitis C and their anti-HCV seronegative spouses were enrolled. RESULTS: The mean follow-up period was 45.9 months. Antibodies to HCV (anti-HCV) and HCV-RNA were tested for in each seronegative spouse every year. Seroconversion of anti-HCV occurred in only one spouse, 2 years after enrollment, with a concomitant acute hepatitis. This subject and his spouse were infected with HCV genotype 1b. Nucleotide sequence comparison of the hypervariable region of their HCV genomes showed a homology of 98%. Further phylogenetic analysis suggested that they had virtually the same isolate. Accordingly, the annual risk of interspousal transmission of HCV infection was 0.23% per year. CONCLUSIONS: These findings suggest a low incidence of interspousal transmission of HCV; however, the risk may be cumulative and such couples should be educated to avoid HCV infection from their spouses.

Disease Transmission, Infectious↗

PubMed2000

Efficacy of consensus interferon in the treatment of chronic hepatitis C.

BACKGROUND AND AIMS: Consensus interferon (CIFN) is a newly developed type I interferon. The aim of this study was to investigate the safety and efficacy of CIFN in the treatment of patients with chronic hepatitis C and to determine the predictors for sustained response. METHODS: Patients were randomized to receive 3 micrograms or 9 micrograms CIFN three times a week for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum transaminase levels and disappearance of serum hepatitis C virus (HCV)-RNA at the end of treatment and at 24 weeks after stopping treatment. Histologic response was defined as a decrease of at least two points in the Knodell necroinflammatory score at week 48 and was compared with baseline. RESULTS: There were no serious adverse effects related to CIFN therapy. Overall, 44% of patients receiving 3 micrograms and 48% of patients receiving 9 micrograms had normalization of serum transaminase levels and disappearance of HCV viremia at the end of treatment. At 24 weeks after stopping treatment, 16% of patients in receiving 9 micrograms and 12% of patients receiving 3 micrograms had sustained responses. The histologic responses in patients receiving 9 micrograms and those receiving 3 micrograms were 60% and 36%, respectively. The necroinflammatory score was significantly reduced from baseline to week 48 in both groups. In addition, bodyweight < 60 kg and pretreatment serum HCV-RNA level < 0.5 MEq/mL can serve as predictors for sustained response to CIFN treatment. CONCLUSIONS: These findings suggest that 9 micrograms CIFN is safe and effective in the treatment of patients with chronic hepatitis C.

Adult↗

PubMed2000

Incidence and clinical presentation of posttransfusion TT virus infection in prospectively followed transfusion recipients: emphasis on its relevance to hepatitis.

BACKGROUND: A novel transfusion-transmissible human DNA virus, TT virus (TTV), has been discovered recently. An attempt was made to determine the incidence and clinical outcome of TTV infection in recipients of blood transfusion. STUDY DESIGN AND METHODS: Serial serum samples collected as part of a prospective study of posttransfusion hepatitis were examined for TTV DNA by a nested PCR assay. RESULTS: Among 150 adults undergoing cardiac surgery, posttransfusion specimens from 59 individuals were positive for TTV DNA. Pretransfusion sera were found to be positive in 13 of these individuals. Therefore, 46 (33.6%) of the 137 previously uninfected patients developed new TTV viremia after transfusion. Among the 46 patients, 3 were coinfected with HCV, 5 were coinfected with HGV, and 38 were infected with TTV alone. No apparent symptoms or signs were noted in the 38 patients infected by TTV alone or the 5 infected with HGV plus TTV. The average peak serum ALT activity was 31 IU per L, with persistently normal levels in 34 of the 38 patients with TTV infection alone. In 8 other patients who subsequently developed well-documented non-A-G hepatitis, 3 were positive for TTV (3/8 vs. 46/137, p = 0.8). In 12 patients followed for more than 1 year, TTV viremia persisted in every case. CONCLUSION: In this population, TTV is transmitted by transfusion to approximately 30 percent of patients who undergo cardiac surgery. Most of the infections appear to become persistent. Despite the high prevalence rate, TTV does not appear to cause hepatitis on its own.

Adult↗

PubMed2000

Vascular anatomic variations in second toe transfers.

To devise a new classification of vascular variations in second toe transfer we analyzed the anatomic details of the first dorsal metatarsal artery in 304 cases of second toe transplantation and the venous structure in 200 cases. According to location, the arterial vascularity was classified as superficial (18% of cases), intramuscular (54%), inframuscular (23%), and absent (5%). According to diameter, it was classified into large (16%), medium (64%), and small (20%). Based on branching pattern, the artery was classified into ramifying type (88%), main trunk (4%), and fine branch type (8%). The venous drainage of the second toe was categorized as greater saphenous vein main trunk type, greater saphenous vein fine branch type, dorsal digital vein main trunk type, and dorsal digital vein fine branch type. Variations of the first dorsal metatarsal artery are common. Classification should be done according to its location, diameter, and branching pattern at the toe web. Regardless of location, big vessels entering the second toe are the most important attribute for successful outcome.

Adolescent↗

PubMed2000

Interspousal transmission of TT virus: low efficiency and lack of apparent risk factors.

BACKGROUND: The TT virus (TTV) is a newly identified human DNA virus and little is known about its non-parenteral transmission. The aim of the present study was to explore the prevalence of TTV infection in spouses of index cases and the related risk factors. METHODS: Serum TTV-DNA was studied in spouses of 41 subjects with TT viremia. For couples in which both husband and wife had TT viremia, nucleotide sequences of the open reading frame-1 region were analyzed by phylogenetic tree constructions. RESULTS: Three (7%) of 41 spouses were positive for TTV-DNA. No differences were noted between index patients with seropositive spouses and those without seropositive spouses with regard to clinical characteristics, including parenteral risk factors and exposure duration. Nucleotide sequence comparison and phylogenetic tree analysis of the viral genome in three TTV-infected couples revealed the isolates to be closely related in two, with a homology of 97 and 98%, respectively. CONCLUSIONS: These results suggest that interspousal transmission of TTV does occur; however,the efficiency of transmission is low compared with hepatitis C virus and GB virus-C. There are no apparent risk factors for transmission between spouses and further studies are needed to clarify other modes of non-parenteral transmission.

Adult↗

PubMed1999

Characterization of monoclonal antibodies against hepatitis C virus nonstructural protein 3: different antigenic determinants from human B cells.

The nonstructural (NS3) region protein of hepatitis C virus (HCV) possesses major B-cell epitopes that induce antibodies after infection. To elucidate further the characteristics of these B cells and their role in the immune regulation of HCV infection, T9 (portion of NS3 region, amino acids [a.a.] 1188-1493)-specific monoclonal antibodies were derived and mapped for B-cell antigenic determinants with recombinant proteins. A total of 10 T9-specific hybridomas were generated and tested for B-cell antigenic determinants. To analyze the B-cell antigenic determinants, eight recombinant proteins including NS3-e (a.a. 1175-1334), NS3-a' (a.a. 1175-1250), NS3-a (a.a. 1251-1334), NS3-b (a.a. 1323-1412), NS3-c (a.a. 1407-1499), NS3-a/b (a.a. 1251-1412), NS3-bc (a.a. 1323-1499), and NS3-abc (a.a. 1251-1499) encoded by NS3-region internal clones were expressed and tested for immunoblotting. The data suggested IgG hybridomas recognized NS3-a, NS3-a', or NS3-b protein by immunoblotting. By contrast, the NS3-e protein bears the major antigenic determinant recognized by human sera. Half of the hybridomas were found to react with protein NS3-a', which is not a major B-cell antigenic determinant in humans. These data suggested that conformational epitopes in vivo may be important for B-cell recognition.

Animals↗

PubMed1999

Prevalence and implication of TT virus infection: minimal role in patients with non-A-E hepatitis in Taiwan.

TT virus (TTV) is a newly identified human DNA virus and little is known about its clinical significance. The aim of the study was to explore the prevalence of TTV infection in different risk populations and in patients with various liver diseases. Viral DNA was studied in 190 high-risk individuals, 97 household contacts, 52 patients with acute hepatitis A, 32 patients with non-A-E hepatitis including 13 fulminant hepatitis, 200 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 100 patients with chronic hepatitis C, and 100 healthy adults. TTV infection was more frequent in high-risk groups (26-70%), patients with acute or fulminant non-A-E hepatitis (42-45%), and hepatitis C carriers (36%) than in healthy adults (10%) and hepatitis B carriers (15%). However, most of subjects with TTV infection alone had no or only mild hepatitis, and the same rate of TTV DNA in pre-hepatitis serum samples and constant serum TTV titers during hepatitis episodes were observed in two patients with acute non-A-E hepatitis. Phylogenetic analysis of the Taiwanese TTV isolates showed genetic heterogeneity and most (68%) isolates were TTV type 1. No particular strain was found to be associated with fulminant non-A-E hepatitis.

Acute Disease↗

PubMed1999

Liver and peripheral blood mononuclear cells are not major sites for GB virus-C/hepatitis G virus replication.

The pathogenesis and replication sites of GB virus-C/hepatitis G virus (GBV-C/HGV) in humans remain unclear. The presence of GBV-C/HGV and hepatitis C virus (HCV) RNA sequences in matched serum, peripheral blood mononuclear cells (PBMC) and liver samples in 10 patients with GBV-C/HGV infection, 8 of whom were coinfected with HCV was explored. Positive- and negative-strand GBV-C/HGV and HCV RNA were detected by strand-specific reverse-transcription polymerase chain reaction (RT-PCR), and virus titers were quantified by competitive PCRs. Positive-strand GBV-C/HGV RNA was detected in 7 of 10 PBMC samples of the patients with serum GBV-C/HGV RNA, but negative-strand GBV-C/HGV RNA was not found in these cells. Positive-strand GBV-C/HGV RNA was found in 9 liver samples, and 2 (22%) of them also had negative strand. In contrast, negative-strand HCV RNA was frequently found in PBMC and liver samples. A positive correlation between the titer of viral RNA in liver tissue and that in serum sample was demonstrated in HCV infection, but not in GBV-C/HGV infection. These findings suggest that liver and PBMC are not the major replication sites for GBV-C/HGV and that GBV-C/HGV is not a primary hepatotropic virus.

Adult↗