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Biomedical subjects

C L Lai

Publications and source records attributed to C L Lai.

At least 109 records · Page 6Linked to original sources

Pathogenic role of hepatitis B virus in hepatitis B surface antigen-negative decompensated cirrhosis.

This study was conducted to determine the rate of detection of serum hepatitis B virus (HBV) DNA in hepatitis B surface antigen (HBsAg)-negative decompensated cirrhotic patients who had hepatitis B core and/or surface antibodies (anti-HBc and/or anti-HBs), and to compare the outcome of HBsAg-positive cirrhotic patients who did or did not clear HBsAg during follow-up. Six (5%) of 121 HBsAg-positive cirrhotic patients lost HBsAg after 0.2 to 17.1 years (mean, 9.1 +/- 6.2 yr) of follow-up. The cumulative rates of loss of HBsAg at 1, 5, 10, and 15 years were, respectively, 1.3%, 1.3%, 7.4%, and 44.5%. Compared with the patients who remained HBsAg-positive, those who lost HBsAg had milder disease at presentation and significantly longer survival. Of the patients who lost HBsAg, 83% had improvement in liver function after the loss of HBsAg, and all were alive at the time of writing (0.8 to 5.7 years after loss of HBsAg), whereas 27% of those who remained HBsAg-positive had died and 29% had deterioration in liver function. The rate of detection of serum HBV DNA by polymerase chain reaction (PCR) assay was higher in HBsAg-positive cirrhotic patients who lost HBsAg:67% versus cirrhotic patients who had no previous history of chronic HBV infection; 16% (cryptogenic) and 29% (hepatitis C virus and/or alcohol-induced liver disease). In summary, we found that using PCR, serum HBV DNA can be detected in 28% of HBsAg-negative cirrhotic patients who were studied, but the pathogenic significance of such small amounts of virus is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Diagnostic value of ultrasonically guided lung aspiration in pneumonia].

To determine the diagnostic value of ultrasonic lung aspiration for patients with pneumonia, 60 patients with a tentative diagnosis of pneumonia were included in this study. After recording ultrasonographic findings, lung aspiration was done with a spinal needle and aspirated specimens were sent for Papanicolaou, May-Giemsa, acid fast, and Gram stains. The remaining specimens were sent for bacterial, mycobacterial and fungal culture. Twelve patients were excluded from the study because of the final diagnosis of non-infectious pulmonary diseases. In 28 cases of bacterial pneumonia, the diagnostic sensitivity of smear was 50% and culture 61%. The overall sensitivity of needle aspiration and culture was 71%. In 11 cases of bacterial pneumonia with a negative bacterial culture result, 7 cases were afebrile at the time of examination. To increase the diagnostic yield, needle aspiration should be performed at the acute stage of bacterial pneumonia. In 15 cases of pulmonary tuberculosis, the diagnostic rate of acid-fast smear was 47% and mycobacterial culture was 46%. The overall sensitivity of smear and culture was 60%. The diagnostic rate of needle biopsy was 75% and cytologic examination was 77%. Needle biopsy and cytologic examination enhanced the diagnostic rate of sputum-negative pulmonary tuberculosis. Cryptococcosis was documented by smear and needle biopsy in all of the five cases of cryptococcosis. Cryptococcosis is not easily detected by routine cytologic examination, and clinical information is still necessary to enhance the diagnostic rate. Our results show that ultrasonically guided lung aspiration is a technique with a high diagnostic yield and a low complication rate for various types of pneumonia. It is especially useful for patients without satisfactory clinical responses or without accurate microbiologic diagnosis.

Adult↗

Clinicopathologic features of hepatitis C virus infection in renal allograft recipients.

The clinicopathologic features, the natural history, and the prognostic indicators of hepatitis C virus (HCV)-related liver disease in renal allograft recipients have not been well defined. Among 220 renal allograft recipients, 21 were seropositive for HCV RNA, which persisted on prospective follow-up for 40 months. Elevations in alanine aminotransferase and alkaline phosphatase were noted after renal transplantation in 15 (71.4%) and 9 (42.9%) patients, respectively, with 11 (52.4%) showing recurrent or persistent abnormalities. Mortality from liver failure was noted in 1 patient. Persistence of abnormal liver biochemistry was associated with an early onset of biochemical derangement after transplantation, and a longer dialysis duration (P < 0.05). HCV-related liver pathology was assessed in 13 patients by histologic scoring with respect to "hepatitic activity," "bile duct damage," and "architectural abnormality," adding up to a "total" score. Six (46.2%) of 13 initial liver biopsies showed significant chronic liver disease. Liver histology correlated with mean alanine aminotransferase and alkaline phosphatase levels after renal transplantation, and was more severe in patients with persistent biochemical abnormalities. Early onset of abnormal liver biochemistry after transplantation and persistently abnormal biochemistry were independent predictors of worse total and activity scores (P < 0.05). Renal transplant recipients demonstrated lower activity scores when compared with nonimmunosuppressed subjects with chronic hepatitis C (P = 0.03). HCV RNA was detectable in all 23 liver specimens tested. We conclude that significant, potentially life-threatening liver pathology manifests in about half of renal transplant recipients with chronic HCV infection. Liver histology correlates with the longitudinal biochemical profile. Patients with early onset of biochemical abnormalities and persistently deranged liver biochemistry are at risk of developing severe liver disease.

Adult↗

Hepatic expression of interferon-alpha in chronic hepatitis B virus infection.

Hepatic expression of interferon-alpha (IFN-alpha) was examined by immunohistochemistry in 90 Chinese patients (M/F 67:23, age: 14-69) with a spectrum of hepatitis B virus (HBV)-related chronic liver diseases. Immunoreactive IFN-alpha was detected in sinusoidal cells in 79 patients (88%) and in mononuclear cells in 59 patients (65.6%). Patients with active liver diseases (chronic active hepatitis, active cirrhosis, N = 55) had a higher level of IFN-alpha expression compared to patients with inactive histology (N = 35; sinusoidal cells, P < 0.01; mononuclear cells, P < 0.01). Cytoplasmic HBsAg, nuclear HBcAg, and cytoplasmic HBcAg were detected in 79 (88%), 42 (47%), and 23 (27%) patients respectively. Expression of IFN-alpha in mononuclear cells correlated with the expression of cytoplasmic HBcAg (P < 0.05) but not with nuclear HBcAg or cytoplasmic HBsAg. When the patients were divided into four different phases according to the natural history of chronic HBV infection, patients in the active liver disease phase had higher IFN-alpha expression compared to the immunotolerant and late phase patients (P < 0.01). Using double immunohistochemical staining, both IFN-alpha and cytoplasmic HBcAg were frequently detected near inflammatory infiltrates but no correlation existed between the hepatic expression of HBsAg and IFN-alpha. These data indicate that IFN-alpha is expressed in the liver in HBV-related active liver diseases and that the reported suboptimal production of IFN-alpha by PBMC in HBV-related chronic active liver diseases may be due to a redistribution of the IFN-alpha-producing mononuclear cells into the liver, the site of inflammation.

Adolescent↗

Female children respond to recombinant hepatitis B vaccine with a higher titre than male.

One-hundred and eighty Chinese children [age range 5 months to 12 years, seronegative for all hepatitis B virus (HBV) markers] of parents seropositive for HBV surface antigen (HBsAg) were randomized to receive doses of either 10 or 20 micrograms of recombinant yeast-derived HBV vaccine at intervals of 0, 1, and 6 months. Six children defaulted and three other children (1.7 per cent) seroconverted to anti-HBc positivity without detectable HBsAg in the serum. All other children attained an anti-HBs titre of > 10 mlU/ml after three doses. Both 10 and 20 micrograms/dose regime gave a similar geometric mean titre (GMT) of anti-HBs. Children aged 0-4 responded with a similar titre compared with children aged > 4. Female children responded with a significantly higher GMT than male children and this was due to a high proportion of female children with higher peak titres. No major side-effects were encountered. We conclude that recombinant HB vaccine is highly immunogenic, well tolerated and equally effective with doses of both 10 and 20 micrograms and that girls responded with a higher anti-HBs titre compared with boys.

Child↗

Five-year follow-up of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine vs. plasma-derived vaccine in children: immunogenicity and anamnestic responses.

In a prospective randomized trial, 318 children aged between 3 mo and 11 yr who were negative for all hepatitis B markers were randomized to receive two 5-micrograms doses of hepatitis B recombinant DNA yeast vaccine at 0 and 1 mo (group 1), three 5-micrograms doses of hepatitis B recombinant DNA yeast vaccine at 0, 1 and 6 mo (group 2) or three 10-micrograms doses of plasma-derived hepatitis B vaccine (group 3). The HBs antibody response rate at 8 mo was between 93% and 99%; it was still 75% to 87% at 5 yr in all three groups. Geometric mean titers at 1 yr were 83, 1,085 and 858 mIU/ml in groups 1, 2 and 3, respectively. These values had decreased after 5 yr to 47, 131 and 250 mIU/ml. Subjects in group 1 showed a significantly less proportional drop in geometric mean titer at the fifth year than did subjects in group 2 (p = 0.05) or group 3 (p = 0.015). None of the children developed HBc antibody, even after 5 yr of follow-up. We noted 42 episodes of significantly increased HBs antibody titers, probably due to anamnestic response, even when the titers had dropped to low levels. The mean age at which anamnestic response occurred was 8.7 yr.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

The hepatitis C virus genome: a guide to its conserved sequences and candidate epitopes.

A comprehensive analysis of reported hepatitis C virus genomic sequences comprising 151 partial or complete nucleotide sequences and 159 partial or complete amino acid sequences revealed an irregular composition of conserved and variable regions. There were but eight conserved nucleotide sequences, none outside the 5' noncoding and structural regions. A search among conserved amino acid sequences revealed 14 candidate B-cell epitopes, which were chosen mainly on the basis of their hydrophilicity profiles. Twenty five candidate T-cell epitopes were selected according to the criteria of absolute conservation of amino acid sequence, together with characteristic sequence motifs, amphipathic helical structure, or both. Conserved peptide sequences, with the characteristics of both B- and T-cell epitopes, were identified in the nonstructural 5 (NS5) region of the genome.

Amino Acid Sequence↗

Treatment of inoperable hepatocellular carcinoma by transcatheter arterial chemoembolization using an emulsion of cisplatin in iodized oil and gelfoam.

Eighty patients with inoperable hepatocellular carcinoma (HCC) were treated by transcatheter arterial chemoembolization using an emulsion of Lipiodol and Cisplatin. In 59 patients, gelfoam embolization was also given. The tumour size ranged from 0.5 cm to 33 cm in maximum diameter with the median diameter being 8 cm. The chemoembolization sessions were repeated every 1 1/2 to 3 months. The number of sessions the patients underwent varied from 1 to 11, with the mean number of sessions being 3.7. The HCC either disappeared completely or decreased in size in 44 patients (55%). In patients having an HCC of 12 cm or less in size, 31 out of 41 (75.6%) who had the addition of gelfoam demonstrated decrease in tumour size, while seven out of 11 (63.6%) without the addition of gelfoam demonstrated decrease in tumour size. In patients having an HCC of more than 12 cm in size, only six out of 18 (33.3%) who had the addition of gelfoam demonstrated reduction in tumour size and none of the 10 patients without the addition of gelfoam responded. Thus, HCCs of 12 cm or less in size responded better than larger ones to chemoembolization (P < 0.0001) while the addition of gelfoam enhanced the response (P = 0.039). The 1 year survival rate for the 80 patients was 53% and the 2 years survival rate was 38%. The median survival was 13 months. For patients having an HCC of 12 cm or less in size, the 1 year and 2 year survival rates were 69% and 47% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Re-evaluation of alpha-interferon treatment of chronic hepatitis B using polymerase chain reaction.

To re-evaluate the efficacy of 3 treatment trials involving 272 Chinese patients with chronic hepatitis B virus infection, serial serum samples were tested from 60 patients treated with alpha-interferon with or without prednisone priming and 12 control patients, who were negative for hepatitis B virus deoxyribonucleic acid using dot-blot hybridization. Serial samples were tested using nested polymerase chain reaction with primer sets chosen from the surface and core antigen coding regions. The 19 patients who did not show persistent serological change remained hepatitis B virus deoxyribonucleic acid positive using the polymerase chain reaction assay. Three of the 4 patients (75%) who lost hepatitis B surface antigen and 9 of 51 (17.6%) who lost hepatitis B e antigen became negative from 0 to 60 months after the e-seroconversion. All patients negative for the polymerase chain reaction assay had normal transaminase levels. Pooling the 3 trials together, 11 of 188 (5.9%) treated patients and 1 of 84 (1.2%) control patients became hepatitis B virus deoxyribonucleic acid negative. The difference was not statistically significant. As assayed by the polymerase chain reaction assay, patients who were treated with alpha-interferon with or without steroid priming and lost hepatitis B e antigen within 12 months were more likely to subsequently lose the virus completely from the serum (11 of 33) than those who lost hepatitis B e antigen after 12 months (none of 13; p = 0.029).

Base Sequence↗

Relationship between intrahepatic expression of hepatitis B viral antigens and histology in Chinese patients with chronic hepatitis B virus infection.

Hepatic cellular and subcellular expression of hepatitis B virus (HBV) antigens--HBsAg, HBcAg, and HBeAg--in 143 Chinese patients with chronic HBV infection were studied by immunohistochemical techniques. Nuclear expression of HBcAg and nuclear and cytoplasmic expression of HBeAg showed a secular trend decreasing from the carrier state and chronic persistent hepatitis (CPH), through chronic active hepatitis (CAH), to cirrhosis with or without hepatocellular carcinoma. In contrast, cytoplasmic HBcAg expression was significantly greater in patients with CPH and CAH (P < .0108). In addition, cytoplasmic HBcAg correlated significantly with lobular activity, portal inflammation, and hepatitic activity (P < or = .007). Expression of cytoplasmic HBcAg also exceeded cytoplasmic HBeAg and nuclear HBcAg in liver specimens showing significant damage (P < .038). HBsAg, however, showed no secular trend and was not related to liver histology. The authors' findings support the theory that HBcAg is also the viral target antigen for immune-mediated liver damage in Chinese patients with chronic HBV infection.

Adolescent↗

The variability of the hepatitis B virus genome: statistical analysis and biological implications.

A statistical analysis of the nucleotide sequence variability in 14 published hepatitis B virus (HBV) genomes was carried out using parametric and nonparametric methods. A parametric statistical model revealed that the different regions of the genome differed significantly in their variability. The conclusion was supported by a nonparametric kernel-density model of the HBV genome. Genes S, C, and P, region X, the precore region, and the pre-S2/pre-S1 regions were ranked in order of increasing variability. In many instances, conserved regions of the genome identified with sequences of known function in HBV biology. However, other characterized regions (such as pre-S) showed much variability despite the involvement of their encoded peptides in specific functions. Point mutations that may result in the formation of stop codons and amino acid changes may affect the clinical picture of HBV infection and may be reflected in atypical serological patterns.

Consensus Sequence↗

Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial.

To evaluate the clinical efficacy of interferon-alpha in hepatocellular carcinoma, 71 adult Chinese patients with histologically proven inoperable hepatocellular carcinoma were randomized to receive recombinant interferon-alpha 2a (50 x 10(6) IU/m2) intramuscularly three times a week (n = 35) or no antitumor therapy (n = 36). The survival of interferon-alpha-treated patients was significantly better than that of patients who received no antitumor therapy (p = 0.0471); median lengths of survival were 14.5 and 7.5 wk, respectively. Objective tumor regression greater than 50% was observed in 31.4% (11 of 35) of patients receiving interferon-alpha. Interferon-alpha induced tumor regression greater than 50% in 11 (31.4%) patients. Compared with the group receiving no antitumor therapy, the interferon-alpha therapy group had more tumor regression (p < 0.0001) and less tumor progression (p = 0.001). This high-dose interferon-alpha therapy was relatively well tolerated; only 34.3% of patients required reduction of dosage by one third or one half because of persistent fatigue. Two patients with diabetes mellitus (one also had tabes dorsalis) exhibited mental deterioration that might have been partially attributable to interferon-alpha therapy. We conclude that interferon-alpha is useful in a proportion of Chinese patients with inoperable hepatocellular carcinoma, both in prolonging survival and in inducing tumor regression.

Adult↗

Seroepidemiological survey of hepatitis E in Hong Kong by recombinant-based enzyme immunoassays.

The agent that causes the enterally transmitted form of non-A, non-B hepatitis has been cloned and called hepatitis E virus (HEV). We have carried out a seroepidemiological survey on the prevalence of hepatitis E in Hong Kong. In a retrospective study, serum from 394 patients with acute viral hepatitis and 355 healthy subjects was tested for antibodies to HEV (anti-HEV) with a recombinant-based enzyme immunoassay. 65 (16.5%) patients with hepatitis were positive for IgM anti-HEV and 23 (5.8%) were also positive for IgM anti-HEV. Of 18 patients diagnosed as having acute non-A, non-B, non-C hepatitis, 6 were IgM anti-HEV positive. 17 (6%) patients in whom acute hepatitis A was diagnosed were also infected with HEV. None of 70 patients with acute hepatitis B or C or exacerbation of chronic hepatitis B was IgM anti-HEV positive. 57 (16.1%) of the healthy subjects were positive for IgG anti-HEV. The prevalence of IgG anti-HEV was higher in subjects over 20 years old than in younger subjects (24% vs 4%, p < 0.0001). IgG anti-HEV was detected in 26% of subjects who were positive for IgG antibody to HAV and in 7% of those negative for that antibody (p < 0.0001). We demonstrated the validity of the recombinant-based enzyme immunoassays for the diagnosis of hepatitis E. Our results suggest that hepatitis E accounts for a third of non-A, non-B, non-C hepatitis in Hong Kong and that coinfection of hepatitis A and E can occur.

Acute Disease↗

Significance of isolated anti-HBc seropositivity by ELISA: implications and the role of radioimmunoassay.

Hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) are excellent markers for HBV infection and its immunity. The significance of isolated antibody to HBV core antigen (anti-HBc) seropositivity is not certain. To elucidate this, sera from 638 Chinese adult subjects, aged 18-52 years, seronegative for both HBsAg and anti-HBs, were tested for anti-HBc. Fifty-one (8%) were found to have an isolated anti-HBc seropositivity by ELISA, and all were negative for IgM-anti-HBc. The anti-HBc persisted in all subjects who attended follow-up for hepatitis B vaccination (n = 48) for a period of 8 months. These 48 subjects received 3 doses of hepatitis B vaccine (HB-VAX, 10 micrograms or 20 micrograms) at 0, 1, and 6 months: 72.9% developed a primary anti-HBs response (suggestive of a false-positive anti-HBc seropositivity), 4.2% developed an anamnestic or secondary anti-HBs response, and 22.9% did not develop an anti-HBs response. Increasing the cutoff point of the ELISA or reconfirmation with radioimmunoassay (RIA) reduced only a minor half of the false positives. This low specificity of anti-HBc ELISA/RIA, together with the high rate of anti-HBs response to hepatitis B vaccine, indicates that subjects with isolated anti-HBc seropositivity should be included in vaccination programs.

Adolescent↗

Fulminant hepatic failure in nonmetastatic renal cell carcinoma.

Paraneoplastic manifestations including reversible abnormal serum liver biochemistry are known to occur in at least one third of patients with renal cell carcinoma. This hepatic dysfunction has always been regarded as benign in nature and attributed to reactive nonspecific hepatitis. In contrast to this belief, we report here a more devastating course of an asymptomatic patient with nonmetastatic renal cell carcinoma which ranged from mere serum liver biochemistry derangement to a fatal end with fulminant hepatic failure within 10 days. To our knowledge, this is the first report of such a case.

Aged↗

Maintenance therapy for duodenal ulcer: a randomized controlled comparison of seven forms of treatment.

PURPOSE: We performed a randomized controlled trial to compare the efficacy of seven forms of maintenance treatment of duodenal ulcer, including a mealtime regimen of antacids. PATIENTS AND METHODS: We randomized 785 patients with healed duodenal ulcer to receive: (1) no treatment; (2) mealtime antacids with an acid-neutralizing capacity of 80 mmol/day; (3) an antidepressant, trimipramine 25 mg; (4) an anticholinergic, pirenzepine 50 mg; (5) cimetidine 200 mg; (6) cimetidine 400 mg; (7) ranitidine 150 mg; or (8) sucralfate 1 g twice a day. Symptomatology and side effects were assessed every 2 months and endoscopy was performed every 4 months up to 1 year. RESULTS: The patients were comparable in the majority of clinical characteristics before entry. The cumulative percentages of patients with relapse of ulcers at 12 months by life-table analysis were 61% with no treatment, 38% with mealtime antacids, 60% with trimipramine, 52% with pirenzepine, 46% with cimetidine 200 mg, 44% with cimetidine 400 mg, 30% with ranitidine 150 mg, and 40% with sucralfate. Cimetidine 400 mg, antacids, ranitidine 150 mg, and sucralfate were significantly better than no treatment and the other forms of treatment. Ranitidine was significantly better than antacids, cimetidine, and sucralfate in preventing endoscopically documented duodenal ulcer relapse by multiple comparison at 12 months, but not by life-table analysis nor when symptomatic relapses were compared. No significant difference was detected among antacids, cimetidine, and sucralfate. No major side effects occurred with the seven forms of treatment, but those receiving antacids had the highest incidence of minor adverse events (26%). CONCLUSION: This study suggests that mealtime antacids are as effective as H2-receptor antagonists and sucralfate in the maintenance treatment of duodenal ulcer disease, but have to be taken three times a day and had the highest incidence of reported minor adverse events. The relapse rate was lower with ranitidine than with cimetidine, sucralfate, and antacids, but the difference was small and may not be clinically important.

Adult↗

A controlled trial of interferon with or without prednisone priming for chronic hepatitis B.

In a randomized, controlled trial of recombinant interferon alfa-2b with or without prednisone priming in Chinese adults with chronic hepatitis B virus infection, stratified randomization for pretreatment serum alanine aminotransferase levels was done. Partial or complete antiviral responses were achieved in 17 (21.5%) of 79 treated patients and 3 (8.3%) of 36 controls (P = 0.14). The response to interferon treatment was significantly better in those who had elevated pretreatment transaminase levels and comparable to that reported in white patients [15 (38.5%) of 39 patients compared with 2 (5%) of 40 who had normal pretreatment transaminase levels (P = 0.0005)]. The spontaneous seroconversion rate was also higher among the controls with elevated transaminase levels [3 (18.8%) of 16 compared with 0 of 20 with normal transaminase levels], but this difference was not statistically significant (P = 0.16). Among the interferon-treated patients, prednisone priming appeared to have a marginal benefit over treatment with interferon alone in patients with elevated transaminase levels (43% vs. 33%), but not in those with normal transaminase levels (0% vs. 9.5%). It was confirmed that Chinese patients with normal transaminase levels respond very poorly to interferon alfa therapy. However, the response was significantly better in patients with elevated transaminase levels.

Adult↗

Hepatitis D virus superinfection remains a rare occurrence in non-drug abusers in Hong Kong.

Recent studies from Taiwan reported an increased prevalence of hepatitis D virus (HDV) superinfection as well as a spread of HDV infection to non-drug abusers. We examined the current prevalence of HDV superinfection in Hong Kong by testing sera from a large cohort of patients with acute and chronic hepatitis B virus (HBV) infection, collected between January 1988 and December 1990, for IgG antibody to HDV (anti-HDV). Anti-HDV was detected in 13 (93%) of 14 parenteral drug abusers who had HBV-related chronic liver disease. However, anti-HDV was detected in only one (0.15%) of 664 non-drug abusers who had chronic HBV infection and none of 31% patients with acute hepatitis B. We concluded that HDV superinfection remains a rare occurrence in non-drug abusers in Hong Kong.

Cohort Studies↗