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Biomedical subjects

M J Tong

Publications and source records attributed to M J Tong.

At least 37 records · Page 2Linked to original sources
PubMed1997

Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group.

This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-alpha2b). Patients were randomized to receive CIFN at doses of 3 microg or 9 microg, or 15 microg IFN-alpha2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-microg dose than the 3-microg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-microg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-microg IFN-alpha2b cohort. However, patients receiving 9 microg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 microg IFN-alpha2b over the course of treatment (P < .01). Similarly, analysis of patients infected with HCV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-microg CIFN group when compared with the 15-microg IFN-alpha2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 microg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-microg IFN-alpha2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 microg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.

Adult↗
PubMed1997

Prediction of response during interferon alfa 2b therapy in chronic hepatitis C patients using viral and biochemical characteristics: a comparison.

Patients with chronic hepatitis C (n = 103) were treated for 24 weeks with interferon alfa 2b and followed up for 24 weeks after cessation of therapy (week 48). When hepatitis C virus (HCV) RNA at week 48 was used to assess interferon response, 15 (14.6%) were virological complete responders, and all have remained HCV RNA negative for a mean of 3 years. At week 48, 3 of 15 virological complete responders had elevated alanine transaminase (ALT) values. When serum ALT level was used at week 48 to determine response to interferon, 20 (19.4%) were biochemical complete responders. However, 8 of the 20 patients with normal ALT levels were HCV RNA positive at week 48, and 7 of these individuals have had a recurrence of elevated ALT levels within 3 years after cessation of treatment. These findings indicate that measurement of HCV RNA was more accurate than ALT in determining true responses to interferon therapy. Identification of nonresponders early during the course of interferon treatment showed that an elevated ALT level at week 12 was 92% predictive (odds ratio 3.7) but misidentified 33% (5 of 15) of the patients who were virological complete responders at week 48. In contrast, a positive HCV RNA at week 12 of treatment was 98% predictive (odds ratio 35.5) and misidentified only 6.7% (1 of 15) of the virological complete responders. Thus, positive HCV RNA at week 12 of therapy was more accurate in identifying eventual virological nonresponders than measurement of ALT at this time. Termination of interferon therapy in patients who were HCV RNA positive at week 12 would result in a 27% reduction in the direct medical costs and keep patients from undergoing unnecessary treatment. Therefore, testing for HCV RNA at week 12 to identify nonresponders and then discontinuing their treatment is practical, cost-efficient and beneficial both to patients and to third-party payers.

Adolescent↗
PubMed1997

Detection of antibodies to hepatitis E virus in patients with autoimmune chronic active hepatitis and primary biliary cirrhosis.

BACKGROUND: Viral hepatitis E (HIV) frequently causes epidemic outbreaks in many developing countries. It is also present in developed countries as imported cases. The role of hepatitis A virus as trigger for autoimmune chronic hepatitis has been demonstrated, and it has been suggested that this may also apply to HEV. METHODS: The presence of anti-HEV antibodies in serum samples from patients with autoimmune chronic active hepatitis (n = 52) and with primary biliary cirrhosis (n = 25) was investigated using an Abbott assay and a peptide-based test. RESULTS: Anti-HEV antibodies were detected with the Abbott test in 13% (7 of 52) of the patients with autoimmune chronic active hepatitis, but not of these were positive in the synthetic peptide-based test. CONCLUSION: These findings indicate the HEV is not associated with primary biliary cirrhosis but may be implicated in some cases of autoimmune chronic active hepatitis.

Autoimmune Diseases↗
PubMed1996

Comparison of three different hybridization assays in the quantitative measurement of serum hepatitis B virus DNA.

The measurement of hepatitis B virus (HBV) DNA, is important for monitoring and evaluating the efficacy of anti-viral agents in the treatment of patients with chronic hepatitis B. Three different hybridization assays for quantitative measurement of HBV DNA: direct membrane (dot-blot) hybridization, liquid hybridization (Abbott HBV DNA assay) and branched DNA signal amplification assay (Quantiplex, Chiron), were applied to 114 serial serum samples obtained from 13 patients with chronic active hepatitis B who had received ribavirin 600 mg daily for four weeks. Among the three assays, the correlation was found to be highest between Quantiplex and Abbott HBV DNA assay (r = 0.71, p < 0.01), moderate between Quantiplex and dot-blot hybridization (r = 0.58, p < 0.01) and lowest between dot-blot hybridization and Abbott HBV DNA assay (r = 0.27, p < 0.01). Quantiplex detected 107 (94%) of 114 specimens and was the most sensitive assay. All specimens positive by dot-blot hybridization and Abbott HBV DNA assays were detected positive by Quantiplex. The Dot-blot hybridization assay detected all 89 (100%) specimens with a high HBV DNA level (> or = 10 million genome equivalent (Meq)/ml by Quantiplex), but detected only 7 (50%) of 14 specimens with a low HBV DNA level (< 10 Meq/ml). The Abbott HBV DNA assay detected 85 (95%) of 89 specimens with a high HBV DNA level, but detected only 3 (17%) of 18 specimens with a low HBV DNA level. Among 7 negative specimens in the Quantiplex assay, 2 were detected positive by polymerase chain reaction. In conclusion, Quantiplex assay was more sensitive than Abbott HBV DNA assay and dot-blot hybridization assay for quantitative measurement of serum HBV DNA and can be used in the evaluation of the therapeutic drug effect on chronic hepatitis B patients.

Alanine Transaminase↗
PubMed1996

Clinical sequelae of hepatitis C acquired from injection drug use.

We determined the course of hepatitis C infection in 125 patients with a history of injection drug use. The mean age at presentation was 43.5 years, and the mean age of initiating injection drug use was 23.1 years. Fatigue and hepatomegaly were present in as many as 60% of patients. All had antibodies to the hepatitis C recombinant protein C25, and 99% were positive for hepatitis C virus RNA. After the initial workup, 33 (26%) patients had chronic hepatitis, 46 (37%) had chronic active hepatitis, 45 (36%) had cirrhosis, and 1 (0.8%) presented hepatocellular carcinoma. During follow-up, hepatocellular carcinoma developed in 2 other patients. In 74 patients with a 1-year history of injection drug use, the mean number of years to the development of chronic hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma were 15.6, 17.6, 19.4, and 26.3 years, respectively. In this subgroup of patients, heavy alcohol abuse did not appear to influence the progression of liver disease. The 2-year case-fatality rate was 2%. Our findings indicate that hepatitis C is a progressive disease, but only a few died during the average 20.4 years after the initiation of injection drug use. Antiviral treatment to eradicate the virus and halt the progression of disease is indicated in this group of patients.

Adult↗
PubMed1996

Evaluation of hepatitis B and C viral markers: clinical significance in Asian and Caucasian patients with hepatocellular carcinoma in the United States of America.

In order to evaluate the roles of hepatitis B virus (HBV) and hepatitis C virus (HCV) and their clinical significance in Asian-American and Caucasian patients with hepatocellular carcinoma (HCC) in the USA, 110 HCC patients, seen in a community-based teaching hospital in the Los Angeles area over a 10 year period, were enrolled. Seventy-nine (72%) patients were Asian-American and 31 (28%) were Caucasians. Of the 110 HCC patients, 69 (63%) were positive for serum hepatitis B surface antigen (HBsAg), 26 (24%) were positive for serum antibody to hepatitis C virus (anti-HCV), five (all Asian-Americans) were positive for both markers; 11 (10%) patients had a history of alcoholism. HBsAg was detected in 63 (80%) Asian-American patients, significantly higher than in the six (19%) Caucasian HCC patients (P < 0.01). Anti-HCV was detected in 10 (32%) Caucasian and in 16 (20%) Asian-American HCC patients (P > 0.05). Among Asian-American HCC patients, anti-HCV was more prevalent in those who were HBsAg-negative than in the HBsAg-positive patients (69 vs 8%; P < 0.01). A history of alcoholism was obtained in nine (29%) Caucasian HCC patients, significantly higher than in the two (3%) Asian-American HCC patients (P < 0.05). Comparing HCC patients with positive HBsAg and with anti-HCV, HBsAg-positive HCC patients were younger, Asian-Americans and predominantly male; 38% had a family history of liver disease. In contrast, anti-HCV-positive HCC patients were older by nearly a decade and 46% had a history of blood transfusion. Using a stepwise logistic regression analysis, Asian race and patient age < 50 years were found to be independent predictors for HBsAg-positivity, while a history of blood transfusion was the only predictor for anti-HCV-positivity in HCC patients. There was no significant difference in the rate of cirrhosis, serum levels of alpha-fetoprotein and survival between HBsAg-positive and anti-HCV-positive HCC patients. In conclusion, chronic HBV infection was the major aetiological factor in Asian-American HCC patients, while chronic HCV infection and alcoholism were major aetiological factors in Caucasian HCC patients in the USA.

Age Factors↗
PubMed1995

Clinical outcomes after transfusion-associated hepatitis C.

BACKGROUND: The extent of serious complications in people who have acquired chronic hepatitis C infection after a blood transfusion is unclear. METHODS: We studied 131 patients with chronic post-transfusion hepatitis C who were referred to our center between February 1980 and June 1994. Eighty-two other patients were excluded because they had multiple transfusions, hemophilia, intravenous drug use, human immunodeficiency virus infection, hepatitis B infection, hemochromatosis, or alcoholic liver disease. Liver biopsies were performed in 101 patients; biopsies were not performed in the other 30 patients, all with signs of cirrhosis, because the results of coagulation tests were abnormal. RESULTS: The mean age of the patients was 57 years (range, 21 to 81) at the time of our initial evaluation. The mean age at the time of the blood transfusion was 35 years (range, 1 to 76). The mean duration of follow-up after presentation to us was 3.9 years (range, 1 to 15). Eighty-eight of the patients (67.2 percent) initially had fatigue, and 89 (67.9 percent) had hepatomegaly. Twenty-seven patients (20.6 percent) initially had chronic hepatitis, 30 (22.9 percent) had chronic active hepatitis, 67 (51.1 percent) had cirrhosis, and 7 (5.3 percent) had hepatocellular carcinoma. Hepatocellular carcinoma developed in an additional seven patients an average of 36 months (range, 7 to 121) after the initial visit. During follow-up, 20 patients (15.3 percent) died: 8 from complications of cirrhosis (1 after a liver transplantation); 11 from hepatocellular carcinoma; and 1, with chronic active hepatitis, from pneumonia. CONCLUSIONS: In a group of patients seen at a referral center, chronic post-transfusion hepatitis C was a progressive disease and, in some patients, led to death from either liver failure or hepatocellular carcinoma.

Adult↗
PubMed1995

Evaluation of sexual transmission in patients with chronic hepatitis C infection.

BACKGROUND: The transmission of hepatitis C virus (HCV) by parenteral exposure is well documented. However, a proportion of patients with acute or chronic HCV infection have an unknown source of infection. OBJECTIVES: The purpose of this study is to evaluate the role of sexual transmission in HCV infection. STUDY DESIGN: 68 patients (median age, 50 years) with chronic hepatitis C and their spouses were tested for the presence of antibody to HCV (anti-HCV) by multi-antigen and chimeric C25 antigen enzyme immunoassays and for HCV RNA by the polymerase chain reaction. Information on sexual activity and risk factors for HCV infection were obtained from all couples via a questionnaire. RESULTS: All index patients were positive for both anti-HCV and HCV RNA. Antibody to HCV was detected in four (5.9%) of their spouses. One anti-HCV-positive spouse had a history of blood transfusion while the other three (4.4%, 95% CI = 1.5-12.2%) had no known risk factors for HCV infection and thus may have been exposed to HCV via sexual transmission. Two of these 3 spouses had positive serum HCV RNA and had identical HCV genotype to the index patients. The length of sexual exposure was significantly longer in the couples who both were anti-HCV-positive than in patients whose spouses were anti-HCV negative (median: 25 vs. 10 years, P = 0.02, Mann-Whitney test). In our 68 index patients, 96% had antibodies to the recombinant proteins from the C22 (core) and C33C (NS3) regions, and 82% and 76% had antibodies to the proteins from the NS5 and C100-3 (NS4) regions. Identical anti-HCV profiles were noted in two of the four anti-HCV-positive couples. CONCLUSIONS: Our results indicate that sexual transmission, although uncommon, should be considered as a risk factor for HCV infection, especially in spouses who have had long-term intimate relationships with a chronic hepatitis C patient.

Journal Article↗
PubMed1995

A pilot, open-labelled, phase II study using oral ribavirin in the treatment of patients with chronic active hepatitis B.

BACKGROUND: Ribavirin is a synthetic purine nucleoside with demonstrated antiviral activity against several DNA and RNA viruses. OBJECTIVES: An open-labelled pilot study to evaluate the safety and effect of ribavirin in the treatment of patients with chronic active hepatitis B (CAH-B). STUDY DESIGN: 24 CAH-B patients were treated with oral ribavirin 1200 mg daily in 3 divided doses for 4 weeks. Biochemical and virological parameters were monitored at regular interval during and after treatment. RESULTS: The serum hepatitis B e antigen (HBeAg) and HBV DNA measured by dot-blot hybridization were positive in all patients before treatment. At the end of 4 weeks of therapy, the HBV DNA levels decreased in 15 (63%) patients and became undetectable in 1 (4%) of these individuals. The mean HBV DNA decreased from 288+/-78 pg/ml at baseline to 219+/-79 pg/ml at the end of the 4 weeks of treatment (p = 0.046). Eight weeks after cessation of treatment, HBV DNA was undetectable in 10 (42%) patients, and the mean HBV DNA was 46+/-23 pg/ml (p < 0.01 when compared to mean baseline value). Seven (29%) patients seroconverted from HBeAg positive to anti-HBe positive but no patients lost hepatitis B surface antigen (HBsAg) during the 8 weeks of follow-up. At the end of 4 weeks of ribavirin treatment, serum levels of alanine aminotransferase (ALT) decreased in all but 1 patient; only 1 patient normalized serum ALT at this time. The mean serum ALT decreased significantly from 416+/-72 IU/l at baseline to 179+/-35 IU/l at the end of 4 weeks of treatment (p = 0.001). Eight weeks after cessation of therapy, the mean serum ALT value was 151+/-32 IU/l (p < 0.001 when compared to mean baseline value) and 5 (21%) patients normalized serum ALT at this time. During ribavirin treatment, the main side effect was a decrease in the hemoglobin level which returned to the pretreatment level in each instance within 2 months after discontinuance of therapy. CONCLUSIONS: Results of this pilot study indicated that oral ribavirin was well tolerated in CAH-B patients and resulted in lowering of serum ALT and HBV DNA values. A randomized controlled trial is needed to fully evaluate the beneficial effects of ribavirin in CAH-B patients.

Journal Article↗
PubMed1995

Clinical manifestations of hepatitis A: recent experience in a community teaching hospital.

A study of the clinical profile of 59 patients who presented with hepatitis A virus infection showed that dark urine, fatigue, gastrointestinal complaints, and fever were the most common presenting symptoms. The most frequent physical findings were hepatomegaly and jaundice. The mean presenting laboratory tests included total bilirubin of 5 mg/dL, alkaline phosphatase of 269 units/L, and serum aspartate aminotransferase and alanine aminotransferase levels of 1442 mIU/mL and 1952 mIU/mL, respectively. Atypical manifestations included relapse, cholestasis, rash, and arthralgia. Two patients presented with hepatitis A and concomitant type I autoimmune chronic hepatitis, and both required immunosuppressive therapy. Five patients who presented with hepatitis A were pregnant, and during follow-up, none of their infants developed elevated serum transaminase values or had detectable IgM anti-HAV antibody. All 59 patients experienced complete clinical and biochemical recovery within 6 months after onset of illness.

Acute Disease↗
PubMed1994

Nucleotide sequence analysis of the precore region in patients with spontaneous reactivation of chronic hepatitis B.

The role of HBV precore mutations in the spontaneous reactivation of chronic hepatitis B (CHB) is currently unknown. We studied 10 patients with CHB; five were HBeAg+ (group I) and five were anti-HBe+ (group II). All 10 had spontaneous reactivation of CHB as defined by the appearance of clinical symptoms along with an increase of serum ALT activity at least 5X above baseline values, in the absence of any other known causes of liver disease or CHB reactivation. The precore (87 nt) and proximal core (81 nt) regions were sequenced after PCR amplification. From each patient three serum samples studied: one 3-12 months before, one during, and one six months after reactivation. Prior to reactivation, none of the group I patients harbored an HBV strain having a mutation that prevented HBeAg synthesis; however, 2/5 developed such a mutation during reactivation (G to A transition at nt 1896). Among the group II patients, three harbored an HBeAg defective mutant both before and during reactivation; after six months, two of these three patients were HBV DNA negative in serum by PCR. Several other sequence polymorphisms, some of which changed the predicted amino acid sequence, were either present initially or developed during reactivation. In conclusion, in this small group of CHB patients who were HBeAg+ spontaneous reactivation was accompanied in some cases by a shift to an HBeAg defective mutant, while in patients who were anti-HBe+, such mutations were frequently present prior to reactivation. In patients already harboring precore defective mutants, spontaneous reactivation may precede an attenuation of viral replication.

Adult↗
PubMed1994

Naturally occurring hepatitis B virus mutants with deletions in the core promoter region.

A novel class of hepatitis B virus mutants in patients with chronic hepatitis B is described. The predicted effect of the mutations is to disrupt the X open reading frame. The location of the genetic alterations within the putative precore promoter also suggests that they may ameliorate precore transcription, which would provide an alternate mechanism for HBeAg(-) escape variation. Definitive conclusions regarding the effects of these mutations must await additional in vitro and in vivo studies.

Adult↗
PubMed1994

Evidence for hepatitis C viral infection in patients with primary hepatocellular carcinoma.

In testing for antibodies to the hepatitis C virus (anti-HCV) in 112 patients with primary hepatocellular carcinoma, 10 of 33 white patients (30%) and 15 of 79 Asian patients (19%) had a positive response to the antibody. The antibody profile to individual hepatitis C viral antigens and the presence of circulating hepatitis C viral RNA were determined in the 25 patients. The anti-HCV antibodies most frequently detected were toward the antigens from the core (C22) and NS3 regions. Serum hepatitis C viral RNA was present in 17 of the 25 patients (68%), and these patients tended to have serum levels of alanine and aspartate aminotransferases higher than those patients without viremia (136 +/- 22 U per liter versus 64 +/- 11 U per liter and 161 +/- 26 U per liter versus 79 +/- 14 U per liter, respectively, both P < .05). Of the 15 Asian patients with hepatocellular carcinoma and anti-HCV, 4 (27%) had coexisting hepatitis B surface antigen (HBsAg) and 13 (87%) had antibodies to either hepatitis B core or surface antigen. Of the 10 white patients with anti-HCV, however, only 1 (10%) had hepatitis B virus antibodies (P < .01). Among 4 Asian patients with coexisting anti-HCV and HBsAg, 1 was found to have serum hepatitis B viral DNA and the other 3 had hepatitis C viral RNA. A history of blood transfusion was obtained from 12 of the 25 patients with anti-HCV (48%); 20 (80%) had coexisting cirrhosis. Our findings support the hypothesis that hepatitis C virus is an important etiologic agent in the development of primary hepatocellular carcinoma in both white and Asian patients in the United States.

Adult↗
PubMed1994

Hepatitis B virus infection in Asian Americans.

This article summarizes studies on hepatitis B in the Asian American population and includes prevalence rates among different Asian subgroups, routes of transmission, and sequelae of both perinatal and childhood-acquired hepatitis B virus infection. Rationale for use of hepatitis B immune globulin and hepatitis B vaccine for Asian infants and vaccine for children and seronegative adults is discussed also. Chronic hepatitis B, cirrhosis, and primary hepatocellular carcinoma in adults and screening for early detection of liver cancer are reviewed.

Adult↗
PubMed1993

Risk factors for hepatitis C virus infection among health care personnel in a community hospital.

OBJECTIVE: To determine the prevalence of and risk factors for antibody to the hepatitis C virus in hospital employees. METHODS: Retrospective testing of serum samples obtained from 1677 hospital employees during a prehepatitis B vaccination program in a private teaching community hospital. RESULTS: Twenty-three employees (1.4%) were found to have antibody to hepatitis C virus. The prevalence of antibody to hepatitis C virus was higher in blacks (3.4%) than in whites (1.1%, p = 0.03) and Hispanics (2.6%, p = 0.88). In a logistic regression model, factors significantly associated with antibody to hepatitis C virus seropositivity included antibody to hepatitis B core antigen (p = 0.002), a history of blood transfusion (p = 0.03), and needlestick injuries (p = 0.04). CONCLUSION: Although the prevalence of antibody to hepatitis C virus in health care workers was not high, needlestick injuries were associated with an increased risk for acquiring hepatitis C virus infection.

California↗
PubMed1993

Hepatitis A vaccination.

The safety and immunogenicity of an inactivated hepatitis A virus vaccine were assessed in 101 healthy adults. Seronegative persons with normal serum aminotransferase levels were grouped according to age: Group 1 (n = 24) and group 3 (n = 22) were between 18 and 40 years of age, and group 2 (n = 25) and group 4 (n = 30) were older than 40 years. Groups 1 and 2 received vaccine on a 0-, 1-, and 2-month schedule (schedule A), and groups 3 and 4 received the vaccine on a 0-, 1-, and 12-month schedule (schedule B). Of the 101 vaccinated subjects, 98 (97%) seroconverted with antibody titers to hepatitis A virus of > or = 20 IU per liter after the first dose, and all subjects seroconverted after the second dose. The geometric mean titers a month after the third vaccine dose were significantly greater (P < .03) on both schedules for younger subjects (schedule A, 1,743 IU per liter, and schedule B, 7,882 IU per liter) than for older subjects (schedule A, 826 IU per liter, and schedule B, 4,279 IU per liter). Also, the differences in geometric mean titers a month after the third dose were significantly greater (P < .001) for subjects in both age groups on schedule B (group 3, 7,882 IU per liter, and group 4, 4,279 IU per liter) than for those on schedule A (group 1, 1,743 IU per liter, and group 2, 826 IU per liter). The hepatitis A virus was well tolerated, with mild discomfort at the injection site being the main side effect. This vaccine is both safe and highly immunogenic.

Adolescent↗