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Biomedical subjects

M F Yuen

Publications and source records attributed to M F Yuen.

44 records · Page 3Linked to original sources

Natural history of chronic hepatitis B virus infection.

In chronic hepatitis B virus (HBV) infection acquired during adulthood, which is the type mostly seen in the Caucasian population, there is biochemical and histologic regression after HBeAg seroconversion, and the risk of death from hepatitis B-related causes is low. In chronic HBV infection acquired during birth or early childhood, which is the type most commonly seen in the Asian population, there is a prolonged phase of immunotolerance. The immune clearance phase is characterized by multiple acute exacerbations preceeded by elevations in serum HBV DNA levels, HBeAg concentration and HBeAg/anti-HBe immune complexes. Of these patients, 2.4% may develop hepatic decompensation during the stage of HBeAg seroconversion. The development of cirrhosis occurs more frequently in patients with episodes of decompensation and with repeated severe acute exacerbations. However progression to cirrhosis can be relatively silent and can occur even in children. After HBeAg seroconversion, precore and core promotor mutations occur frequently in the Asian population. However, there is little correlation between the occurrence of these mutations and alanine aminotransferase elevation in patients who are positive for anti-HBe. Although cirrhosis develops during the process of HBeAg seroconversion, 68% of the complications of cirrhosis and of hepatocellular carcinoma occur after HBeAg seroconversion. These complications may still occur even after HBsAg seroclearance.

Adult↗

Evaluation of a new referral system for the management of dyspepsia in Hong Kong: role of open-access upper endoscopy.

BACKGROUND: In the management of dyspepsia, upper endoscopy is an important component. In our locality, patients requiring upper endoscopy are conventionally referred to specialist clinics by family physicians. We have introduced the first open-access upper endoscopy service in Hong Kong, which has allowed family physicians to arrange endoscopy without prior specialist consultation. A study on the outcome of open-access upper endoscopy in contrast with the conventional referral system was conducted. METHODS: For patients presenting with dyspepsia, family physicians in our region were given the option to arrange upper endoscopy directly with our Medical Endoscopy Unit in addition to the conventional referral to specialist clinics. The results were compared with those from the specialist clinic. A detailed prospective follow up was performed from June to September 1997 to evaluate the outcome and impact of open-access upper endoscopy. RESULTS: From November 1996 to September 1999, 978 referrals for open-access upper endoscopy were received. The service significantly reduced the waiting time for the procedure by 16 weeks. Open-access upper endoscopy had similar detection rates for peptic ulcers and cancers compared with referrals from specialist clinics. Seventy-five percent of patients did not require further consultation with their family physicians within 2 months after endoscopy. It is a safe and effective procedure in establishing a definitive diagnosis. All family physicians were satisfied with the open-access upper endoscopy service. CONCLUSIONS: This is the first Asian report on this service. Open-access upper endoscopy reduced waiting time from the patient perspective, decreased subsequent consultations with family physicians and reduced referral to specialist clinics as well as increased patient and doctor satisfaction. Both referral systems for endoscopy were similar in terms of the diagnostic yield.

Ambulatory Care Facilities↗

Twelve-year follow-up of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine versus plasma-derived vaccine without booster doses in children.

A total of 318 children were prospectively randomized in group 1 with two 5-microg doses of recombinant vaccine given at 0 and 1 month; in group 2 with three 5-microg doses of recombinant vaccine given at 0, 1, and 6 months; or in group 3 with three doses of plasma-derived vaccine given at 0, 1, and 6 months. Eleven subjects with a hepatitis B surface antigen antibody (anti-HBs) titer of less than 10 mIU/mL at 12 months were given an extra dose of vaccine and were excluded from analysis. No booster doses were given to any other subjects. All children were followed up yearly for the level of anti-HBs titers and for the detection of hepatitis B infection. At the 12th year of follow-up, there were significantly fewer subjects with anti-HBs of 10 mIU/mL or above in group 1 (60.4%) when compared with group 2 (81.4%; P =.0287) and group 3 (79.0%; P =. 0381). The geometric mean titers (GMTs) of subjects of group 1 were significantly lower than those of group 2 and group 3 throughout the 12 years of follow-up. A total of 65 subjects had one or more episodes of anamnestic response. No subject became positive for hepatitis B surface antigen (HBsAg); 2 became positive for hepatitis B core antigen antibody (anti-HBc). In conclusion, the long-term protective immunity was better with three doses of hepatitis B vaccine (either the recombinant or plasma-derived) than with two doses. However, protection from hepatitis B infection could be equally achieved by either two doses or three doses of the vaccine. Booster doses were not necessary, probably because of effective anamnestic response.

Child↗

Mannose binding lectin gene mutations are associated with progression of liver disease in chronic hepatitis B infection.

Mannose-binding lectin (MBL) plays an important role in immune defense. We examined the MBL gene mutations and MBL levels in Chinese hepatitis B and hepatitis C patients with and without symptomatic cirrhosis. We recruited 190 hepatitis B and C patients, and 117 normal Chinese as controls. Serum MBL levels were measured by enzyme-linked immunosorbent assay. MBL gene mutation at codons 52, 54, and 57 was detected by polymerase chain reaction (PCR) assay. In asymptomatic hepatitis B and C patients, there was no increase in codons 52, 54, and 57 mutation, but the MBL levels were significantly lower than those in the controls. Codon 54 mutation rate was increased to 44.4% (P =.007) in symptomatic hepatitis B cirrhosis and 64.3% (P =.0026) in patients with spontaneous bacterial peritonitis (SBP). There was no increase in codon 54 mutation rate in hepatitis B-related hepatocellular carcinoma (HCC). In chronic hepatitis B infection, the odds ratio for an individual with codon 54 mutation to develop cirrhosis was 1.84 (95% CI: 1.21-2. 81) and to develop SBP was 4.58 (95% CI: 1.73-12.16). Chronic hepatitis B and hepatitis C infection lowered the MBL levels, probably by suppressing MBL production. Codon 54 mutation of MBL was associated with progression of disease in chronic hepatitis B infection.

Adolescent↗

Nucleic acid-based cross-linking assay for detection and quantification of hepatitis B virus DNA.

A nucleic acid photo-cross-linking technology was used to develop a direct assay for the quantification of hepatitis B virus (HBV) DNA levels in serum. Cross-linker-modified DNA probes complementary to the viral genomes of the major HBV subtypes were synthesized and used in an assay that could be completed in less than 6 h. The quantification range of the assay, as determined by testing serial dilutions of Eurohep HBV reference standards and cloned HBV DNA, was 5 x 10(5) to 3 x 10(9) molecules of HBV DNA/ml of serum. Within-run and between-run coefficients of variation (CVs) for the assay were 4. 3 and 4.0%, respectively. The assay was used to determine HBV DNA levels in 302 serum samples, and the results were compared to those obtained after testing the same samples with the Chiron branched-DNA (bDNA) assay for HBV DNA. Of the samples tested, 218 were positive for HBV DNA by both assays and 72 gave results below the cutoff for both assays. Of the remaining 12 samples, 10 were positive for HBV DNA by the cross-linking assay only; the 2 other samples were positive by the bDNA assay only. Twenty-eight samples had to be retested by the bDNA assay (CV, >20% between the results obtained from the testing of each sample in duplicate), whereas only three samples required retesting by the cross-linking assay. The correlation between the HBV DNA levels, as measured by the two tests, was very high (r = 0.902; P = 0.01). We conclude that the cross-linking assay is a sensitive and reproducible method for the detection and quantification of HBV DNA levels in serum.

Cross-Linking Reagents↗

Safety of disease modifying anti-rheumatic agents in rheumatoid arthritis patients with chronic viral hepatitis.

OBJECTIVE: To examine the safety of the use of disease modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with chronic viral hepatitis (CVH). METHODS: Records of 600 Chinese patients satisfying the ARA criteria for RA in two rheumatology centers were reviewed. Patients with CVH were studied. Liver enzymes were checked before (baseline) and during DMARD use at 3-month intervals or more frequently if necessary. Drug-episodes (D-Ep), defined as the continuous use of DMARD, singly or in combination, for more than 6 months in a patient, were analysed. Changes in serum liver alanine transaminase (ALT) levels as multiples of the upper range of normal were taken to reflect the severity of hepatotoxicity. Changes of ALT to > or = 1.5 times the upper range of normal if they were measured at baseline or > or = 2 times the upper range of normal if they were measured during and after the use of DMARD were considered as abnormal. Control patients included those with CVH alone (n = 623) or RA without CVH (n = 62) matched for age, sex and D-Ep. RESULTS: 30 RA patients were found to have concomitant CVH. One patient was excluded because of use of NSAID alone (n = 1). Among the 29 patients, 23 were HBsAg +ve and 6 were anti-HCV Ab +ve. A total of 47 D-Ep were analysed. 20/47 (42.6%) of D-Ep in 16/29 (55.2%) RA + CVH patients developed abnormal ALT levels after a mean 1.9-year duration of DMARD use. This was statistically significant when compared with 13/94 (13.8%) of D-Ep which ended with abnormal ALT levels in 13/62 (21%) patients with RA alone (p < 0.0001 for D-Ep which ended up with abnormal ALT, and p < 0.02 for the number of patients who developed abnormal ALT) and 128/623 (20.5%) patients with CVH alone (p < 0.005). 53% (9/17) of hydroxychloroquine (HCQ) D-Ep were associated with an abnormal outcome. Corresponding figures for sulphasalazine (SAZP) and oral or intramuscular gold preparations were 55.6% (5/9) and 0% (0/3) respectively. Two patients on methotrexate, used either singly or in combination, had normal ALT levels throughout the study period. One patient on azathioprine developed reactivation of hepatitis B infection. When D-Ep of the RA + CVH group were further analysed, 16/43 (37.2%) and 4/4 (100%) D-Ep which started with normal and abnormal baseline ALT respectively developed further liver enzyme derangement. CONCLUSION: The use of DMARD in RA + CVH patients is associated with a high incidence of hepatotoxicity. The effect is likely to be synergistic. This includes drugs such as HCQ, which is generally believed to be less hepatotoxic.

Adult↗