Antiviral therapy of the Asian patient with chronic hepatitis B.
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Adult↗
Biomedical subjects
A S Lok
Publications and source records attributed to A S Lok.
Chronic hepatitis C after renal transplantation. Treatment with alpha-interferon.
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Adult↗
Prevalence of hepatitis C virus infection in hemodialysis patients: a longitudinal study comparing the results of RNA and antibody assays.
We longitudinally studied 51 patients from two hemodialysis centers to determine the prevalence of hepatitis C virus infection in hemodialysis patients. Serum samples were tested for antibody to HCV by first- and second-generation enzyme immunoassays and for hepatitis C virus RNA by nested polymerase chain reaction assay. Antibody to hepatitis C virus was detected in the initial serum samples by first-generation enzyme immunoassay and second-generation enzyme immunoassay in 6 (11.8%) and 11 (21.6%) patients, respectively. First-generation enzyme immunoassay had a false-positive rate of 33.3% and a false-negative rate of 63.6%. Hepatitis C virus RNA was found in eight second-generation enzyme immunoassay-positive patients (72.7%) and in one patient negative for antibody to hepatitis C virus (2.5%) giving an overall positivity rate of 17.6%. After 19 mo, antibody to hepatitis C virus was detected in 15 patients (29.4%) on second-generation enzyme immunoassay; hepatitis C virus RNA was found in 13 patients (25.5%). Hepatitis C virus markers persisted in all 12 patients with initial evidence of hepatitis C virus infection. Three patients acquired hepatitis C virus infection during the interim, giving a new infection rate of 4.9% per patient-year. Antibody to hepatitis C virus, hepatitis C virus RNA or both was detected in 55.6% of patients with biochemical changes suggestive of non-A, non-B hepatitis. Of the 15 antibody to hepatitis C virus, second-generation enzyme immunoassay-positive patients, 66.7% had persistently normal serum transaminase levels. In summary, hepatitis C virus infection is common among hemodialysis patients. First-generation enzyme immunoassay is an unreliable assay for antibody to hepatitis C virus in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hepatitis C infection among renal transplant recipients: a comparative study using first- and second-generation anti-HCV EIA and HCV detection by nested PCR.
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Adult↗
Antibody response to core, envelope and nonstructural hepatitis C virus antigens: comparison of immunocompetent and immunosuppressed patients.
Some immunosuppressed patients with hepatitis C virus infection do not have detectable levels of antibody to hepatitis C virus on second-generation enzyme immunoassay. Antibodies to the envelope and nonstructural region 5 proteins have not been examined. Four groups of patients with hepatitis C virus infection were studied: (a) 20 immunocompetent patients, (b) 15 hemodialysis patients, (c) 17 kidney transplant recipients and (d) 3 acute leukemia patients who underwent bone marrow transplantation. Serum samples were tested for antibody to hepatitis C virus with a second-generation enzyme immunoassay and multi-antigen enzyme immunoassays and for hepatitis C virus RNA with a nested polymerase chain reaction assay. All the immunocompetent patients reacted to C25, C22 and C33C; 90% reacted to nonstructural region 5 antigen and 80% reacted to C100-3. Only 55% reacted against yeast-derived e1 and e2 antigens, but all reacted against vaccinia virus--expressed N e1 and e2 antigens, indicating that the envelope epitopes are conformational and glycosylated. Sixty-five percent to 90% of dialysis and kidney transplant patients reacted to C25, C22 and N e1 and e2, but only 12% to 60% reacted to C100-3, C33C and nonstructural region 5 antigen. Diminution or loss of reactivity to hepatitis C virus antigens was observed after kidney and bone marrow transplantation, with C25 and N e1 and e2 less affected. Our data suggest that incorporation of C25 and N e1 and e2 antigens in the assay for antibody to hepatitis C virus would improve the detection of hepatitis C virus infection in immunosuppressed patients.
Antibody Formation↗
Prevention of posttransfusion hepatitis B and C by screening for antibody to hepatitis C virus and antibody to HBcAg.
Screening of blood donors by testing for antibody to HBcAg and antibody to hepatitis C virus is commonly done. However, the applicability of these screening tests may vary depending on the prevalence of hepatitis B virus and hepatitis C virus infection in various populations. We have therefore prospectively evaluated 158 adult patients who received blood or blood products during open-heart surgery in Hong Kong to compare the efficacy of various serological screening tests in the prevention of posttransfusion hepatitis. Serum from five (0.5%) donors was positive for antibody to hepatitis C virus by second-generation enzyme immunoassay; in two, optical-density readings in enzyme immunoassay were greater than 2.0, but only one was positive for hepatitis C virus RNA by reverse transcription-polymerase chain reaction. The latter donor was also positive for antibody to HBcAg and had elevated serum ALT activity. The recipient of a unit of this donor's blood was the only one in whom posttransfusion hepatitis C developed (0.1% per unit transfused). Screening with antibody to hepatitis C virus was more specific than that with antibody to HBcAg or ALT in excluding donors from transmitting hepatitis C (99.6%, 79.4% and 98.8%, respectively). Both the sensitivity and negative predictive value of screening for antibody to hepatitis C virus were 100%, but the positive predictive value was only 20%. Forty-five blood recipients were considered susceptible to hepatitis B virus infection because testing for hepatitis B serology in serum (HBsAg, antibody to HBsAg and antibody to HBcAg) was negative before being transfused. Asymptomatic hepatitis B seroconversion developed in three (6.7%) recipients (1.1% per unit transfused).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
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↗
Recovery from chronic hepatitis B.
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Adult↗
Hepatitis C viremia in patients with hepatitis C virus infection.
Sera from 103 patients were tested for hepatitis C virus RNA by nested polymerase chain reaction assay. Using primers from the highly conserved 5'-untranslated region, we detected hepatitis C virus RNA in 67 (88.2%) of 76 patients positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. Hepatitis C virus RNA was detected in 93% of patients who had been infected for 10 yr or less and in 89% of those who had been infected for longer than 10 yr. Hepatitis C virus RNA was detected in all patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma and in 50% of those with nonspecific reactive hepatitis or inactive cirrhosis. Hepatitis C virus RNA was not detected in sera from 22 patients negative for antibody to hepatitis C virus or in 5 patients positive for antibody to hepatitis C virus by second-generation but not by neutralization enzyme immunoassay. Using primers from the less conserved nonstructural region 4, we detected hepatitis C virus RNA at a lower frequency, in 66% of patients who were positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. The detection rate was higher in patients with frequent parenteral exposure. Our study showed that hepatitis C viremia can be detected in most patients with hepatitis C virus infection, including those with long-standing infection or advanced liver disease.
Base Sequence↗
Interferon treatment for hepatitis B-associated membranous glomerulonephritis in two Chinese children.
Two Chinese boys, aged 3.5 and 5 years, developed nephrotic syndrome and were chronic carriers of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg). Renal biopsy showed membranous glomerulonephritis and liver biopsy showed chronic persistent hepatitis. They were given interferon-alpha-2a at a dose of 5 MU/m2 on alternate days for 12 and 16 weeks after 2 years of persistent nephrotic syndrome. Patient 1 showed complete remission and resolution of hepatosplenomegaly, but his serum remained positive for HBsAg, HBeAg and hepatitis B virus DNA. Patient 2 showed only a transient clinical response and seroconversion from HBeAg to anti-HBe status. Although not always successful, interferon treatment should be considered in severe persistent nephrotic states, since there is at present no satisfactory treatment for this form of glomerulonephropathy.
Biopsy↗
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↗
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↗
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↗
The impact of donor and recipient hepatitis B surface antigen status on liver disease and survival in renal transplant recipients.
Ninety-eight renal transplant recipients who had been followed for 1-6.5 years (median 3.2 years) were reviewed to determine the effect of donor and recipient hepatitis B surface antigen status on the incidence of hepatitis and on patient survival. The cumulative risk of developing hepatitis posttransplant was significantly higher in hepatitis B surface antigen-positive versus hepatitis B surface antigen-negative patients (P = 0.001). Nine (60%) of 15 patients who were hepatitis B surface antigen-positive prior to transplantation, 3 (75%) of 4 patients who became hepatitis B surface antigen-positive after transplantation, and 17 (22%) of 79 patients who were persistently hepatitis B surface antigen-negative developed hepatitis posttransplant. Five hepatitis B surface antigen-negative patients received allografts from hepatitis B surface antigen-positive donors. None of the five, including one who was initially seronegative, became hepatitis B surface antigen-positive posttransplant. Of the four patients who became HBsAg-positive posttransplant, three received kidneys from donors of unknown HBsAg status in China, while one was transplanted with a kidney from a HBsAg-negative donor. In summary, we found that the risk of developing hepatitis after renal transplantation was significantly higher in hepatitis B surface antigen-positive patients. However, both patient and graft survival were similar in hepatitis B surface antigen-positive and hepatitis B surface antigen-negative patients. The transplantation of kidneys from HBsAg-positive donors to HBsAg-negative patients did not result in clinically significant hepatitis or chronic HBsAg carriage. De novo hepatitis B infection may arise from sources other than the kidney itself.
Adult↗
Natural history and control of perinatally acquired hepatitis B virus infection.
Maternal-infant transmission of hepatitis B virus (HBV) infection is estimated to account for 40-50% of HBV carriers in Chinese populations, but is uncommon among other ethnic groups. The high frequency of maternal-infant transmission among Chinese populations is related to the high prevalence of carrier mothers with replicative HBV infection. The natural course of perinatally acquired HBV infection consists of three phases: an initial phase of immune tolerance followed by a phase of immune clearance and then a non-replicative phase. The initial phase of immune tolerance which may last for several decades contributes to the poor response to interferon therapy. The high prevalence of carrier mothers with replicative infection mandates a combination of passive and active prophylaxis for the newborns.
Adult↗
Life events and daily stress in duodenal ulcer disease. A prospective study of patients with active disease and in remission.
Life events and daily stress were assessed in patients with duodenal ulcer, active or in remission, and in matched disease and normal controls. The mean positive life event scores were significantly lower in duodenal ulcer patients than in disease and healthy controls, and lower in patients with active ulcer than in those in remission. The positive scores and total life change scores decreased significantly after 6 months in the control groups and showed no significant variation in the duodenal ulcer group after 6 months. We conclude that the perception of life events, especially positive ones, is associated with duodenal ulcer.
Adult↗