Biomedical subjects

C L Lai

Publications and source records attributed to C L Lai.

At least 127 records · Page 7Linked to original sources

PubMed1992

Histologic changes in Chinese patients with chronic hepatitis B virus infection after interferon-alpha therapy.

To evaluate the histologic effects of interferon-alpha (IFN alpha) therapy on chronic hepatitis B virus (HBV) infection, a semiquantitative study using a modified Knodell's numeric histologic scoring system was performed on paired pre- and post-treatment liver biopsy specimens from 127 adult Chinese patients from two trials of IFN alpha therapy (IFN alpha, n = 86; control, n = 41). The effects of IFN alpha therapy on the hepatic expression of HBV antigens were also determined using immunohistochemical analysis. Serologic response with clearance of HBV e antigen (n = 18) was associated with reduction in lobular activity, periportal piecemeal necrosis, portal inflammation, and total histologic scores. Loss of HBV e antigen also was associated with a reduction in the amount of HBV core antigen in the hepatocytes. In contrast, there was an increase in hepatic expression of HBV surface antigen after IFN alpha therapy. Patients who lost HBV e antigen with IFN alpha therapy were characterized by more severe initial periportal piecemeal necrosis before treatment. These data indicate that (1) serologic response is associated with a reduction in hepatic HBV replication and an improvement in hepatic histology, and (2) patients with severe periportal piecemeal necrosis respond more favorably to IFN alpha therapy.

Antigens, Viral↗

PubMed1992

Precore sequence variation in Chinese isolates of hepatitis B virus.

Direct sequencing of polymerase chain reaction-amplified serum hepatitis B virus (HBV) DNA was used to characterize the precore region of HBV from Chinese patients with chronic hepatitis. Two types of mutually exclusive variants were found in hepatitis B e antigen (HBeAg)-negative patients. The first (M1) contains a substitution from proline to serine at codon 15. A second group were infected with a previously described mutant (M2) containing a translational stop codon. HBeAg-positive patients were infected with the wild-type virus or the M1-containing strain. M2 emerged in patients with wild-type infection after seroconversion to anti-HBe, whereas M1 was present during the HBeAg-positive phase. In those with fluctuating HBe status, there was no correlation between prevailing HBe serology and sequence. There was an association between infection with variants and severe chronic hepatitis. Patients infected with strains containing M1 while HBeAg positive had a worse prognosis after seroconversion to anti-HBe.

Alanine Transaminase↗

PubMed1992

Subclinical hepatocellular carcinoma in Hong Kong Chinese.

Of the 208 Chinese patients with histologically proven hepatocellular carcinoma (HCC) seen during a 5-year period, 191 patients presented with symptomatic HCC and 17 patients with asymptomatic HCC (subclinical HCC, SCHCC) being picked up by alpha-fetoprotein (AFP) screening. Compared with the patients with symptomatic HCC, patients with SCHCC had a better performance status (p less than 0.01), higher serum albumin levels (p less than 0.05) and lower alkaline phosphatase levels (p less than 0.01). In those patients with symptomatic HCC, 4.7% were operable and only 2 patients had a tumour diameter of less than 5 cm. In contrast, patients with SCHCC had a higher operability rate (76.5%, p less than 0.0001) and all had a tumour of less than 5 cm in diameter (p less than 0.0001). Patients with SCHCC, most of whom had their tumour resected, had a better long-term survival (p less than 0.0001). We conclude that patients with SCHCC picked up by AFP serosurveillance have a better performance status, higher operability and better prognosis.

Actuarial Analysis↗

PubMed1992

Thyroid functions in patients treated with interleukin-2 and lymphokine-activated killer cells.

Treatment of malignant disease with interleukin-2 and lymphokine-activated killer cells activates autoreactive T lymphocytes, stimulates release of cytokines and induces expression of HLA-class II antigens by tumour cells. We studied eight patients with hepatocellular carcinoma treated with a total of 16 courses of recombinant human interleukin-2 and lymphokine-activated killer cells and observed them for features of autoimmune thyroid disease. During the course of treatment there were significant decreases in total serum T4 and T3 and free thyroxine levels, but no change in TSH levels when all patients were analysed as a group. This was due to a number of factors including suppression of thyroid hormone release, haemodilution during interleukin-2 infusion and actual removal of thyroid hormones from the circulation during leukapheresis. Thyroid hormones returned to normal levels during resting period. One patient subsequently developed compensated hypothyroidism (normal total T4, total T3 and free T4 but elevated TSH) and four patients had features of 'sick euthyroid syndrome' (low total T4, total T3 or free T4 but normal TSH). None of the patients studied developed antibodies to thyroglobulin or microsomes. In contrast, no abnormality of thyroid function was seen in any of the nine subjects who received no active treatment. In conclusion, thyroid dysfunction was associated with immunotherapy of malignant disease with interleukin-2 and lymphokine-activated killer cells. This may arise from direct hormonal effects of the cytokines on thyroid hormone production.

Adult↗

PubMed1991

Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases.

Three-hundred forty-one HBsAg-positive family members of 152 patients with chronic hepatitis B virus infection (47 asymptomatic carriers, 59 with chronic hepatitis, 17 with cirrhosis and 29 with hepatocellular carcinoma) were prospectively studied to determine the morbidity and mortality from chronic hepatitis B virus infection in the family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases. Most of the family members had no history of acute hepatitis, were asymptomatic and were unaware of their carrier status. However, 5.3% had stigmata of chronic liver disease, 6% had serum ALT levels that exceeded two times the upper limit of normal and 78% of those who had biopsies had chronic hepatitis with or without cirrhosis. During a follow-up period of 12 to 90 mo (median = 39 mo), 3% had symptoms of chronic liver disease; 24% had transient, recurrent or persistent elevation in serum ALT levels, 1.4% had cirrhosis and 1% had hepatocellular carcinoma. Neither hepatocellular carcinoma in the index patient nor a previous history of hepatocellular carcinoma in the family was associated with an increase in the morbidity and mortality from chronic hepatitis B virus infection in the HBsAg-positive family members.

Adolescent↗

PubMed1991

Overestimation of the prevalence of antibody to hepatitis C virus in retrospective studies on stored sera.

Serum samples (1,428) from 1,149 patients with chronic liver diseases and polytransfused subjects were tested for antibody to hepatitis C virus by first-generation enzyme immunoassays. Antibody to hepatitis C virus was detected in 87% of patients with transfusion-related chronic non-A, non-B hepatitis; 17.6% of patients with nonmalignant, chronic hepatitis B virus infection; 37.3% of patients with hepatocellular carcinoma; 14.3% of patients with alcoholic liver diseases; 22.2% of patients with cryptogenic cirrhosis; 76% of intravenous drug abusers; 16.4% of patients on hemodialysis; 1.8% of patients on peritoneal dialysis; 6.2% of kidney transplant recipients; and 3.1% of normal subjects. A high frequency of weakly positive results was found in "aged" samples: 61.9% of antibody to hepatitis C virus-positive patients whose sera had been stored for more than 2 yr had optical densities less than two times the cut-off values in contrast to 7.9% of those whose sera had been stored for less than 2 yr (p less than 0.0001). A significantly lower proportion of patients who had optical densities less than two times the cut-off values were reactive in subsequent samples, 27.5% vs. 87.5% (p less than 0.0001). On retests, only 70% and 56% of sera that were initially positive for antibody to hepatitis C virus remained antibody to hepatitis C virus positive using second-generation enzyme immunoassays and neutralization enzyme immunoassays, respectively. Our results suggest that retrospective studies on stored sera may have overestimated the prevalence of antibody to hepatitis C virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗

PubMed1991

A randomised controlled trial of recombinant interferon-gamma in Chinese patients with chronic hepatitis B virus infection.

Nineteen Chinese patients with chronic hepatitis B virus (HBV) infection, seropositive for HBV e antigen (HBeAg) and HBV DNA on at least three occasions in 6 months, were randomised to receive either recombinant human interferon-gamma (rIFN gamma) 0.1 mg/m2 intramuscularly thrice weekly for 16 weeks (n = 11) or no anti-viral therapy (controls, n = 8). Five patients in the treatment group and four patients in the control group had persistently elevated serum alanine aminotransferases (ALT) of over two times the upper limit of normal before entering into the trial. rIFN gamma had no or minimal inhibitory effect on serum HBV DNA during treatment and no patient developed e-seroconversion or sustained loss of serum HBV DNA. Hepatitic flare, which occurred in a proportion of patients responding successfully to interferon-alpha (IFN alpha) therapy, was not observed with rIFN gamma treatment. Side-effects included pyrexia and mild headache that showed tachyphylaxis and were well tolerated by all patients. In the control group, one patient with elevated pre-entry serum ALT lost serum HBV DNA and seroconverted to anti-HBe. Another patient with elevated ALT lost serum HBV DNA transiently during therapy. In the dose given, rIFN gamma was safe but had no apparent anti-viral effects in Chinese patients with chronic HBV infection.

Adolescent↗

PubMed1991

Current seroepidemiology of hepatitis A in Hong Kong.

The current seroepidemiology of hepatitis A in Hong Kong was examined by testing stored sera from 702 healthy subjects, collected between 1987-1989, for antibody to hepatitis A virus (anti-HAV). The overall prevalence of anti-HAV antibody was 45.6%. There were significant increases in prevalence of anti-HAV antibody with every 10-year increase in age up to age 40. The prevalence of anti-HAV antibody was 24% for subjects below age 30 and 89.2% for those above age 30 (P less than 0.0001). Socioeconomic factors did not appear to have any influence on the prevalence of anti-HAV antibody. In comparison with another study conducted in Hong Kong 10 years ago, the prevalence of anti-HAV antibody in the current study was significantly lower in every age group from 0 to 30 years. In summary, it was shown that HAV infection is no longer highly endemic in Hong Kong. In view of the changing epidemiology, postexposure prophylaxis will be necessary for young adults and children, and hepatitis A vaccine may be indicated for high risk groups when it is generally available.

Adolescent↗

PubMed1991

Effect of omeprazole on duodenal ulcer-associated antral gastritis and Helicobacter pylori.

This study set out to investigate the effects of omeprazole or ranitidine on the progression of antral gastritis and Helicobacter pylori in patients with active duodenal ulcer. A double-blind, double-dummy trial was performed in 270 patients, 241 of whom were studied histologically for the presence of H. pylori. Patients were randomized to receive omeprazole, 10 mg every morning, omeprazole, 20 mg every morning, or ranitidine, 150 mg twice a day, for four weeks. Endoscopy was performed on entry and at weekly intervals during the study; at least two antral biopsies were taken on each occasion to assess the activity and degree of chronic inflammation, as reflected by the degree of polymorphonuclear leukocyte infiltration and mononuclear cell infiltration, respectively. Biopsy specimens also were assessed histologically for H. pylori. The sex, age and maximal acid output were comparable in the three treatment groups. The percentages of patients showing an improvement in the activity of gastritis in the four consecutive weeks of treatment were 9%, 40%, 51%, and 53% for omeprazole, 10 mg (N = 78); 14%, 42%, 49%, and 53% for omeprazole, 20 mg (N = 81); and 2%, 23%, 30%, and 33% for ranitidine, 150 mg twice a day (N = 82) (life table analysis gave P less than 0.01 for both omeprazole regimens compared with ranitidine). The degree of chronic inflammation showed similar changes. The density of H. pylori decreased significantly after treatment with omeprazole, 10 mg or 20 mg, (both, P less than 0.00001) but not with ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Application of hepatitis B virus (HBV) DNA sequence polymorphisms to the study of HBV transmission.

Short sequences in hypervariable regions of the hepatitis B virus (HBV) genome can be used to identify different strains, providing a novel approach to the study of HBV transmission. The nucleotide sequence in positions 2551-2650 (1:EcoRI site) was determined for serum HBV DNA from 96 Chinese children living in Hong Kong and from 38 of their parents. HBV DNA was extracted and sequenced after amplification with the polymerase chain reaction, using as primers oligonucleotides corresponding to two conserved sequences. Among 82 unrelated children, 32 HBV DNA variants were present. One sequence was present in 33 children and 31 variants were found among the other 49. Siblings within each of nine families had the same variant; in three families siblings had different variants. Six of the eight fathers and 28 of the 30 mothers had HBV DNA sequences identical to those of their offspring. A total of 34 variants were found among the 134 individuals. The hypothesis of random assortment of sequences in parents and children was rejected (P less than .00005). Thus, this new approach proves the occurrence of intrafamilial transmission of HBV among Chinese.

Adult↗

PubMed1991

Crescentic IgA glomerulonephritis following interleukin-2 therapy for hepatocellular carcinoma of the liver.

A patient who developed crescentic IgA nephropathy following treatment with recombinant interleukin-2 (rIL2) and lymphokine-activated killer (LAK) cell therapy for hepatocellular carcinoma was reported. Cessation of rIL2 and LAK cell treatment plus plasmapheresis and steroid therapy was successful in achieving partial improvement and stabilization of renal function. This is the first case report of biopsy-documented glomerulonephritis developing after IL2 and LAK cell therapy. This provides indirect in vivo evidence for the role of IL2 in mediating glomerular injury in IgA nephropathy.

Biopsy↗

PubMed1991

Neutrophils in chronic active hepatitis type B.

Liver biopsy specimens from 95 patients with chronic active hepatitis type B were studied to define the incidence of portal tract and/or septal neutrophilic infiltration and its relationship with other morphohistologic factors and with liver function tests. Neutrophils were identified in the portal tracts and fibrous septa in 59 cases (62%), among which 19 cases (20%) showed four or more neutrophils per high-power field. Significant neutrophilic infiltration (greater than 6 per high-power field) was observed in only seven (7.4%) of 95 cases. Multiple-regression analysis revealed that neutrophilic infiltration was significantly associated with marginal duct proliferation, bile duct proliferation, and an elevated alanine aminotransferase level. Applying a partial correlation coefficient, it was shown that neutrophilic infiltration was not related to piecemeal necrosis after controlling for marginal duct proliferation or bile duct proliferation. The findings suggest that in chronic active hepatitis B, while piecemeal necrosis interferes with bile flow at the limiting plate region, marginal duct and bile duct proliferations follow and lead to the accumulation of neutrophils.

Adolescent↗

PubMed1991

Effect of recombinant alpha 2 interferon with or without prednisone in Chinese HBsAg carrier children.

Ninety Chinese hepatitis B surface antigen (HBsAg) carrier children, aged 2-17 years, positive for hepatitis B e antigen (HBeAg) and hepatitis B virus DNA on at least three occasions in 6 months, were randomized into 3 groups. Thirty children received syrup vitamin B complex as control, 29 received 6 weeks of placebo syrup followed by 16 weeks of recombinant alpha 2b-interferon [intron A (rIFN2b)], 5 x 10(6) u/m2 subcutaneously thrice weekly; and 31 received 6 weeks of syrup prednisone (0.6 mg/kg tailed to 0.2 mg/kg) followed by 16 weeks of recombinant alpha 2b-interferon as above. The placebo/prednisone syrup was given on a double-blind basis. At 24 months of follow-up, persistent loss of hepatitis B virus DNA occurred in none of the children in the control group, in one child receiving recombinant alpha 2b-interferon alone, who also seroconverted to anti-HBe and anti-HBs and in five children receiving interferon with steroid priming (p = 0.0571 compared with controls), with four seroconverting to anti-HBe and one also seroconverting to anti-HBs. A rise of transaminases to above twice the upper limit of normal levels during the first 7 months of follow-up occurred in one subject in the control group, four in the group receiving alpha 2b-interferon alone and nine in the group receiving recombinant alpha 2b-interferon with steroid priming (p = 0.0144 compared with controls). Side effects of the steroid were negligible; those of recombinant alpha 2b-interferon were transient and acceptable. We conclude that 6 weeks of prednisone followed by 16 weeks of recombinant alpha 2b-interferon is of use in inducing persistent loss of hepatitis B virus DNA (16.1 per cent) and e-seroconversion (12.9 per cent) in a proportion of Chinese HBsAg carrier children: the prednisone probably enhances the immunomodulatory effect of recombinant alpha 2b-interferon.

Adolescent↗

PubMed1990

Evidence for intrafamilial transmission of hepatitis B virus from sequence analysis of mutant HBV DNAs in two Chinese families.

To study the heterogeneity of hepatitis B virus (HBV) DNAs in Hong Kong, where HBV infection is endemic, serum specimens from 90 HBsAg carrier children were systematically tested with nine oligonucleotide probes representing conserved sequences in the viral genome. In a pair of twins and their cousin (belonging to family H) and an unrelated child (family Y) serum HBV DNA annealed to all but one probe, a sequence located between the core and pre-S regions of the viral genome (positions 2723-2738; EcoRI site 1). Serum from the H twins' aunt and the father and paternal grandparents in the Y family were also HBV DNA-positive. The nucleotide sequences in positions 2701-2800 were analysed. The same point mutation, C to T in position 2735, was present in the HBV DNAs from 7 individuals in the two families. All 4 H family members had the same HBV DNA sequence. The HBV DNA sequences found in the Y daughter, father, and grandfather were identical and they were different from the H family mutant. These results provided evidence at the DNA level of intrafamilial transmission within these Chinese families.

Adolescent↗

PubMed1990

Interferon antibodies may negate the antiviral effects of recombinant alpha-interferon treatment in patients with chronic hepatitis B virus infection.

In a randomized controlled trial of recombinant alpha-2a interferon for chronic hepatitis B, interferon antibodies developed in 21 (39%) of 54 Chinese adults who received IFN. No correlation was observed between sex, age, pretreatment serum ALT level or liver histological findings and the development of interferon antibodies. Antibodies were significantly more likely to develop in patients who received lower doses (2.5 or 5 MU/m2) of alpha-2a interferon than in those who received a higher dose (10 MU/m2): 53% vs. 11% (p = 0.006). The development of interferon antibodies appeared to reverse the initial antiviral response to treatment, with reappearance of hepatitis B virus DNA in serum in 12 patients and HBeAg in three patients. Sustained clearance of HBeAg was achieved in only one (5%) patient but was achieved in seven (21%) patients without interferon antibodies. The mere presence of interferon antibodies did not preclude an antiviral response to interferon therapy, but patients with high titer neutralizing antibodies were less likely to respond. These findings suggest that interferon antibodies may negate the antiviral effects of alpha-2a interferon. A higher incidence of interferon antibodies in Chinese vs. white patients with chronic hepatitis B may contribute to the poorer antiviral response in Chinese patients.

Adult↗

PubMed1990

Acute exacerbations in Chinese patients with chronic hepatitis B virus (HBV) infection. Incidence, predisposing factors and etiology.

Three hundred and eighty-six Chinese patients (262 men and 124 women), age 5-74 years, with chronic hepatitis B virus (HBV) infection were prospectively followed for 1-5 years to determine the incidence, predisposing factors and etiology of acute exacerbations that occurred during the course of chronic HBV infection. Group I consisted of 334 patients with serum alanine aminotransferase (ALT) levels below 200 IU/l at presentation. Of these, 29 (8.7%) patients developed 32 episodes of acute exacerbation during follow-up. The cumulative probabilities of developing exacerbations were 6.3% and 15% at the end of 1 and 4 years, respectively. Group II included 52 patients with ALT levels above 200 IU/l at presentation. Of these, 19 (37%) patients developed 26 episodes of exacerbation during follow-up. The cumulative probabilities of developing eacerbations were 24% and 47% at the end of 1 and 4 years, respectively. In both groups, the probability of developing exacerbations was slightly higher in men and significantly higher in those above the age of 20 and those who were HBeAg positive. Logistic regression analysis showed that HBeAg positivity (p less than 0.00001), elevated ALT levels (greater than 200 IU/l) at presentation (p less than 0.0001) and male sex (p = 0.03) were associated with a significantly higher probability of developing exacerbations. Twenty eight (48%) episodes of exacerbation were accompanied by symptoms of acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

Alpha-interferon treatment in Chinese patients with chronic hepatitis B.

alpha-Interferon has been shown to be the most promising antiviral agent in the treatment of chronic hepatitis B virus infection in Caucasian patients. The experience with recombinant interferon alfa-2a and alfa-2b in four randomized controlled trials in Chinese adults and children is reviewed here. alpha-Interferon alone has little long-term benefit in the treatment of Chinese patients with chronic hepatitis B virus infection, especially in patients who have normal or near normal serum aminotransferase levels. The response in patients with elevated aminotransferase levels appears to be better. The poor antiviral response in patients with normal aminotransferase levels is probably due to immunological tolerance to HBV induced by exposure to the virus in early life. Prednisone pretreatment does not seem to have any additional benefit to using interferon alone in these patients, while the effect in patients with elevated aminotransferase levels remains to be proven.

Adult↗

PubMed1990

A patient with large granular lymphocytosis of unusual phenotype and polymorphic T-cell receptor beta-chain gene rearrangement.

The authors describe a patient with large granular lymphocytosis who presented with fever of unknown origin and jaundice. Immunophenotyping showed that most of the large granular lymphocytes (LGLs) were CD3-, CD16-, and NKH-1 (Leu-19)+ lymphocytes. Lymphocytosis of this subset of LGLs has not been reported. Analysis of T-cell receptor gene showed polymorphic T-cell receptor beta-chain (TCR beta) gene configuration. Functional studies showed reduced natural killer cell function. The clinical course was very aggressive and resistant to chemotherapy. These features again raise the controversial issues of the ontogeny and heterogeneity of LGLs and their relationship to natural killer cells and T-cells.

Adult↗