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Biomedical subjects

C M Chu

Publications and source records attributed to C M Chu.

At least 127 records · Page 7Linked to original sources

The etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers.

To study the etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers, paired sera were collected in acute and convalescence phases for measurement of HBeAg, anti-HBe, hepatitis B virus DNA and anti-delta from 76 adult patients with acute hepatitis who were HBsAg positive but IgM anti-HBc negative or positive only at low titer. None of them were IgM anti-hepatitis A virus positive on admission. Of the 34 patients who were HBeAg positive initially, two (5.9%) were diagnosed as having delta superinfection, and another two (5.9%) were suspected to have non-A, non-B virus superinfection because of a transient decrease of serum hepatitis B virus DNA. The remaining 30 (88.2%) cases were hepatitis B virus DNA negative with or without anti-HBe seroconversion on follow-up. The episodes of acute hepatitis in these cases may represent "immune clearance of HBeAg" or "immune clearance of hepatitis B virus with delayed anti-HBe seroconversion," respectively, in the natural course of chronic hepatitis B virus infection. Of the patients who were anti-HBe positive initially, 23 (54.8%) were diagnosed as having delta superinfection, including eight with de novo seroconversion of anti-delta and 15 with a rising titer of anti-delta; 10 (23.8%) were positive for hepatitis B virus DNA and were considered as reactivation of hepatitis B virus, and the other nine (21.4%) were suspected as having non-A, non-B virus superinfection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Studies on the composition of the mononuclear cell infiltrates in liver from patients with chronic active delta hepatitis.

To evaluate the immune process involved in the pathogenesis of liver cell damage in chronic hepatitis delta virus infection, a panel of monoclonal antibodies against pan T cells (Leu 4), inducer/helper T cells (Leu 3a+3b), suppressor/cytotoxic T cells (Leu 2a), B cells (Leu 12), monocytes/macrophages (Leu M3) and NK/K cells Leu 7) was used to characterize the subsets of the mononuclear cell infiltrates in livers from 12 patients with chronic type D hepatitis, with special emphasis on the areas of periportal piecemeal necrosis and intralobular necrosis. A control group of 12 patients with chronic type B hepatitis was also studied for comparison. The results revealed that the livers from patients with chronic type D hepatitis showed a prominent mononuclear cell infiltration in portal/periportal and intralobular areas. Furthermore, the vast majority of the mononuclear cell infiltrates in liver were T cells, which constituted more than 80% of the cells in the areas of periportal piecemeal necrosis and intralobular necrosis and about 60% of the cells in the portal tract, whereas B cells, monocytes/macrophages and NK/K cells were relatively uncommon. Among T cell populations, the inducer/helper T cells were predominant in the portal were predominant in the areas of piecemeal necrosis and intralobular necrosis. The distribution of the mononuclear cell subsets in relation to the different topographical areas of the liver in patients with chronic type B hepatitis was essentially the same as that observed in chronic type D hepatitis. Our findings therefore suggest that T cell-mediated immunity might play a role in the pathogenesis of chronic type D hepatitis, similar to that suggested for chronic type B hepatitis.

Adult↗

Prevalence and significance of intrahepatic hepatitis delta virus antigen expression in HBeAg-negative patients with chronic type-B hepatitis in Taiwan.

A consecutive series of 97 HBeAg-negative patients with chronic type-B hepatitis, who were not drug addicts or hemophiliacs, were examined for the prevalence of intrahepatic expression of hepatitis delta virus (HDV) antigen (HDAg) by direct immunofluorescence. The clinical and histological features were compared between those with and without intrahepatic HDAg expression. Intrahepatic HDAg expression was detected in 15 (15.5%) of the 97 patients. All of the 15 were males between 18 and 71 years of age. Each had elevated SGPT levels, with 46.8% being greater than 10 times normal and 73.4% greater than five times normal. Histological study revealed chronic lobular hepatitis in nine and chronic active hepatitis in six, including two with cirrhosis. Compared to the 82 patients without intrahepatic HDAg expression, no difference in the age (34.1 +/- 14.3 vs 36.7 +/- 10.8) and sex (15:0 vs 72:10) distribution was evident, but greater biochemical and histological activity was present in HDV-positive patients.

Adult↗

Serum levels of soluble Tac peptide in acute and chronic hepatitis B virus infection.

Serum-soluble Tac peptide was measured by an enzyme-linked immunosorbent assay in 12 patients with acute type B hepatitis, 33 patients with chronic type B hepatitis, and 15 age- and sex-matched controls. All 12 patients with acute type B hepatitis had elevated levels of soluble Tac peptide with a mean (+/- SD) of 1527 +/- 432 U/ml, significantly higher than that of normal controls (264 +/- 74 U/ml) or patients with chronic type B hepatitis (646 +/- 399 U/ml). Serial follow-up showed that serum levels of soluble Tac peptide tended to return to normal 2-4 months after onset of acute hepatitis along with the normalization of alanine aminotransferase and seroconversion of hepatitis B surface antigen (HBsAg) to anti-HBs. Patients with chronic type B hepatitis also had significantly higher levels of soluble Tac peptide than normal controls, although only 63.6% (21/33) of them had a level greater than the upper limit of normal. Serum levels of soluble Tac peptide in patients with chronic type B hepatitis varied considerably with the inflammatity in liver. The hepatitis B e antigen (HBeAg)-positive patients with chronic active liver disease had significantly higher levels of soluble Tac peptide (928 +/- 424 U/ml) than HBeAg-positive (412 +/- 146 U/ml) or anti-HBe-positive (424 +/- 175 U/ml) patients with chronic persistent hepatitis or minimal histological change. In addition, there was a significant positive correlation between serum levels of soluble Tac peptide and alanine aminotransferase. These findings suggested that activation of T cells might play an important role in the pathogenesis of acute and chronic type B hepatitis. Assay of serum-soluble Tac peptide might provide a simple and useful means to better understand the immune mechanisms of acute and chronic hepatitis B virus infection.

Adolescent↗

Natural course of patients with chronic type B hepatitis following acute hepatitis delta virus superinfection.

A 6-96-month prospective follow-up study on the natural course of chronic type B hepatitis after contracting acute hepatitis delta virus (HDV) superinfection was conducted in 30 patients with clear-cut onset of acute HDV superinfection (HDV group). Thirty patients with acute exacerbation without evidence of HDV infection, and well matched in terms of age, sex and hepatitis B e antigen/antibody status, served as the control group. The clinical and biochemical presentations tended to be more severe in the HDV group. More patients in the HDV group had persistent abnormal liver biochemical tests (69% vs 47%) and progressed to chronic active hepatitis (46% vs 20%) or cirrhosis (9.4%/year vs 5.2%/year), but the differences were not significant statistically. The results suggest that HDV superinfection induces slow progression of liver disease. However, in the early stage, the impact of HDV superinfection is not particularly different from that of the acute exacerbation unrelated to HDV in patients with chronic type B hepatitis.

Adult↗

Natural course after the development of cirrhosis in patients with chronic type B hepatitis: a prospective study.

To examine the early stage of the natural course of liver cirrhosis, a prospective follow-up study was conducted in a series of 76 patients with recent development of cirrhosis during the course of chronic type B hepatitis. During a mean follow-up period of 34.4 months, 45 episodes of acute exacerbation were recorded; the majority of the episodes occurred within 2 years after entry. The calculated annual incidence of acute exacerbation was significantly higher in patients seropositive for hepatitis B e antigen (HBeAg) and/or hepatitis B virus (HBV)-DNA (25.9%) than in those without these markers (11.9%). Three-fourths of the acute exacerbations were attributable to the reactivation of HBV. Spontaneous HBeAg seroconversion to anti-HBe also occurred in the early phase, but less than 30% of the events were preceded by acute exacerbation. Late hepatitis B surface antigen clearance occurred in two patients. Hepatic decompensation, esophageal variceal bleeding and hepatocellular carcinoma developed relatively late in the course of the disease with a calculated annual incidence of 2.3%, 2.3% and 2.8%, respectively. Seven patients (9.2%) died of hepatic failure or variceal bleeding, usually more than 3 years after entry. The estimated 5-year survival rate was 80%. The results suggest that the natural events of chronic HBV infection, including exacerbation, seroconversion and its sequelae could occur after the development of cirrhosis. In addition, these events might be responsible for the clinicopathological changes and the outcomes of these cirrhotic patients.

Adult↗

Treatment of chronic type B hepatitis in Southeast Asia.

In Southeast Asia, 15 to 20 percent of the population are hepatitis B surface antigen carriers. The majority of these carriers have chronic hepatitis and would progress to cirrhosis or hepatocellular carcinoma at an annual incidence of 2 percent and 1 percent, respectively. Previous studies from Southeast Asia suggested that immunosuppressive therapy could be harmful, or at best of no value, and antiviral treatment with vidarabine, picibanil, or even interferon was also unsatisfactory. Currently, a randomized controlled trial of human lymphoblastoid interferon, with or without prednisolone pretreatment, versus placebo in patients with hepatitis B core antigen in the liver and hepatitis B e antigen in the serum is being conducted. Forty-five patients (29 receiving interferon, 16 receiving placebo) have been entered in the trial for at least two months. Actuarial analysis shows that the response to interferon therapy was better than that to placebo. Although flu-like symptoms, hair loss, and body weight loss were seen, no side effect requiring specific treatment has been encountered. These preliminary results suggest that human lymphoblastoid interferon is effective and safe in Oriental patients.

Asia, Southeastern↗

Different implications of stigmata of recent hemorrhage in gastric and duodenal ulcers.

A prospective study was conducted to evaluate the prognostic value of stigmata of recent hemorrhage in patients with bleeding peptic ulcer. Of 193 patients suffering from peptic ulcer bleeding identified by emergency gastrointestinoscopy, 52 patients were found to have bleeding gastric ulcer (spurt 5, active oozing 9, fresh clot 11, black clot 17, protruding vessel 4, and clear base without stigmata 6); the other 141 had bleeding duodenal ulcer (spurt 5, active oozing 26, fresh clot 43, black clot 23, protruding vessel 15, and clear base without stigmata 31). Patient with continuous bleeding or rebleeding was grouped as unstable bleeders. The rate of unstable bleeders was 39.1% (continuous bleeding 23.9% and rebleeding 15.2%) in patients with gastric ulcer, compared to 9.0% (4.5% and 4.5%) in duodenal ulcer (P less than 0.001). The unstable bleeder rate of ulcers with spurt, active oozing, clot, and protruding vessel was 80%, 44%, 35.7%, and 0%, respectively, in patients with bleeding gastric ulcer; and 33.3%, 19.2%, 6%, and 0%, respectively, in patients with bleeding duodenal ulcer. The data suggest that the stigmata of recent hemorrhage, excluding protruding vessel, has prognostic significance in bleeding gastric ulcer but less in bleeding duodenal ulcer.

Duodenal Ulcer↗

Changes of serum HBV-DNA in relation to serum transaminase level during acute exacerbation in patients with chronic type B hepatitis.

To examine the relationship between changes of serum hepatitis B virus-dexoyribonucleic acid (HBV-DNA) and transaminase levels during acute exacerbation of chronic type B hepatitis, serial serum specimens from 74 patients were assayed for HBV-DNA by slot blot hybridization with 32P-labeled cloned HBV-DNA as probe. Of these patients, serial serum specimens were obtained with an interval of 2-7 days in 22 patients (Group I), 8-14 days in 30 patients (Group II) and 15-30 days in 22 patients (Group III). The peak of serum HBV-DNA was reached shortly before or simultaneously with the maximum elevation of serum alanine transaminase (ALT) in most (greater than 90%) of the acute exacerbations. In contrast, the peak of serum ALT was reached before maximum elevation of serum HBV-DNA in only 13.6% of Group I, 3.3% of Group II and 13.6% of Group III (9.5% of whole series). The results suggest that the increase of serum HBV-DNA is an event preceding, rather than the result of, hepatocytolysis in most of the acute exacerbations occurring in patients with chronic type B hepatitis.

Alanine Transaminase↗

Construction and application of plasmids containing bidirectional promoters of vaccinia virus.

A bidirectional expression vector containing both the 11KD late promoter (p11) and the presumptive 25KD early promoter (p25) was constructed. These bidirectional vectors have been applied to the expression of hepatitis B surface antigen by using one of the promoters for beta-galactosidase as the marker gene and the other one for hepatitis B surface antigen as the target gene.

DNA Restriction Enzymes↗

Acute delta superinfection in a previously unrecognised HBsAg carrier with transient loss of HBsAg simulating acute non-A, non-B hepatitis.

An 18 yr old previously well male Taiwanese was admitted with malaise, anorexia, and jaundice for two weeks. Results of liver tests were compatible with acute hepatitis. On day 1, he was seronegative for HBsAg, IgM anti-HAV, IgM anti-HBc, IgM anti-CMV, and IgM EBV capsid Ab, but positive for anti-delta in association with anti-HBc and anti-HBs. At follow up on day 5 HBsAg converted to positive with decreasing titre of anti-HBs. On day 19, the titre of HBsAg increased concomitantly with loss of anti-HBs. The results of these serological profiles indicated that this patient was a previously unrecognised HBsAg carrier, who developed acute hepatitis delta virus superinfection with transient loss of HBsAg. This phenomenon should be kept in mind in the serodiagnosis of acute viral hepatitis, especially in areas of high HBV prevalence.

Acute Disease↗

Intrahepatic distribution of hepatitis B surface and core antigens in chronic hepatitis B virus infection. Hepatocyte with cytoplasmic/membranous hepatitis B core antigen as a possible target for immune hepatocytolysis.

The intrahepatic distribution of hepatitis B core antigen (HBcAg) and surface antigen (HBsAg) was studied in 32 patients with chronic type B hepatitis, and the results were correlated with the status of hepatitis B e antigen/antibody (HBeAg/anti-HBe) and with the histologic activity of the patients. In HBeAg-positive patients with minor hepatitis activity, HBcAg was distributed mainly in the nuclei, whereas HBsAg was diffusely located on the plasma membrane as well as focally in the cytoplasm. In HBeAg-positive patients with chronic active liver disease, although the distribution pattern of HBsAg in liver remained unchanged, the expression of nuclear HBcAg decreased significantly with concomitant increase in cytoplasmic/membranous HBcAg expression. In HBsAg carriers who were anti-HBe positive, HBcAg was undetectable anywhere, whereas HBsAg could be seen only in the cytoplasm. These results suggest that membranous expression of HBsAg relates closely to active viral replication but is probably not responsible for the observed histologic activities. In contrast, cytoplasmic/membranous expression of HBcAg correlates with high degree of liver inflammatory activity. It is therefore suggested that hepatocytes with cytoplasmic/membranous HBcAg expression might be the target cells for immune hepatocytolysis.

Cell Membrane↗

Diagnosis of acute type B hepatitis by a solid phase u-antibody capture radioimmunoassay for IgM class antibody to hepatitis B core antigen: a diagnostic proposal based on a prospective study.

The diagnostic and prognostic significance of IgM anti-HBc, studied by a solid phase u-antibody capture radioimmunoassay at a serum dilution of 1:4000, was prospectively evaluated in 73 adult patients with acute hepatitis seropositive for hepatitis B surface antigen (HBsAg). Of the 73 cases, 20 (27.4%) cleared their HBsAg within 6 months, while the remaining 53 (72.6%) did not. HBsAg seroconversion to its antibody occurred in 15 (93.8%) of the 16 patients positive for IgM anti-HBc with S/N ratios above 5.0, as did 5 (26.3%) of the 19 with S/N ratios between 2.1 to 5.0, and none (0%) of the 38 negative for IgM anti-HBc (S/N ratios less than 2.1). Therefore, a S/N ratio of IgM anti-HBc above 5.0 is diagnostic for acute type B hepatitis. However, low S/N ratios (2.1-5.0) of IgM anti-HBc were observed in the early stage of some patients with acute type B hepatitis, and would increase to a level greater than 5.0 when assayed again 1-2 weeks later. It was therefore suggested that repeated testing of anti-HBc IgM is mandatory for accurate diagnosis of acute type B hepatitis in patients whose initial serum specimens showed low S/N ratios of IgM anti-HBc. According to this criterion, only 22 (30.1%) of the 73 patients with acute hepatitis seropositive for HBsAg in Taiwan were true acute type B hepatitis, of whom 2 (9.1%) subsequently became chronic HBsAg carriers, while the remaining 51 (69.9%) were chronic HBsAg carriers with other superimposed forms of acute hepatic injury.

Adult↗

Hepatitis delta virus infection in Taiwan.

In Taiwan the prevalence of anti-Delta was low among asymptomatic HBsAg carriers, patients with HCC and acute type B hepatitis, intermediate in HBsAg carriers on hemodialysis, patients with chronic type B hepatitis and liver cirrhosis, particularly HBeAg negative ones, and very high in intravenous drug abusers. It is important to prevent the spread of HDV infection in this hyperendemic area of HBV.

Carrier State↗

Peripheral T-cell subsets in asymptomatic hepatitis B-virus carriers.

To ascertain whether the abnormalities of circulating T-cell subsets in patients with hepatitis B virus (HBV)-related chronic liver diseases represent the primary immunological process or are secondary to liver disease process, peripheral T-cell subsets were analyzed by indirect immunofluorescence using monoclonal antibodies against total T cells (OKT3), T helper/inducer cells (OKT4), and T suppressor/cytotoxic cells (OKT8), in 30 asymptomatic HBV carriers without biochemical or histological evidence of liver disease, and the results were compared to 15 HBV-induced chronic active liver diseases. The results revealed that OKT4/OKT8 ratios were significantly reduced in 15 hepatitis B e antigen (HBeAg)-positive asymptomatic carriers as compared with controls, with decreased OKT4-positive cells and increased OKT8-positive cells, while T-cell subsets and ratios were normal in 15 hepatitis B e antibody (anti-HBe)-positive asymptomatic carriers. The changes of circulating T-cell subsets in 15 HBe-Ag-positive asymptomatic carriers showed no significant difference from those of 15 HBeAg-positive patients with chronic active liver diseases. These findings suggest that the deranged T-cell subsets in chronic HBV infection are not secondary to liver cell damage, but might represent the underlying immunological abnormalities which are closely related to HBeAg/anti-HBe status, and that the pathogenetic mechanism of liver cell damage in chronic HBV infection may not be simply related to circulating T-cell subsets.

Adolescent↗

Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. A prospective study.

A prospective surveillance of hepatocellular carcinoma (HCC) using serum alpha-fetoprotein and high-resolution, linear-array, real-time ultrasonography was carried out in 432 patients with clinicopathologically proven chronic type B hepatitis. During a follow-up period of 6-85 mo (median 23, mean 26.9 +/- 16.8 mo), asymptomatic HCC was identified in 8 patients, with a calculated annual incidence of 826/100,000, and 2768/100,000 for patients over age 35 yr. The relative risk of developing HCC in hepatitis B surface antigen-positive chronic hepatitis patients was 2 when compared to those that were hepatitis B surface antigen-negative, and was 5 when compared in patients over age 35 yr. Hepatocellular carcinomas detected by these methods were in a relatively early stage as most tumors were small, only 50% were associated with cirrhosis, 37.5% were positive for hepatitis B e antibody, and most were still resectable. We, therefore, recommend a combination of alpha-fetoprotein and ultrasonography surveillance in patients with chronic hepatitis in order to improve the chance of early HCC detection as well as the chance for successful resection. In addition, the low incidence of cirrhosis and hepatitis B e antibody in these patients with "early" HCCs and the occurrence of hepatitis B e antigen/hepatitis B e antibody seroconversion after HCC had developed suggest that the development of HCC and progression from hepatitis to cirrhosis were two independent (though related) sequelae of chronic hepatitis B virus infection.

Adolescent↗