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Biomedical subjects

C M Chu

Publications and source records attributed to C M Chu.

At least 91 records · Page 5Linked to original sources
PubMed1995

Simultaneous acute hepatitis B virus and hepatitis C virus infection leading to fulminant hepatitis and subsequent chronic hepatitis C.

A 22-year-old male Taiwanese was admitted to the hospital for acute hepatitis B associated with fulminant hepatic failure. After receiving supportive treatment, the patient's clinical condition improved and the results of liver function tests (including prothrombin time) gradually improved. However, in spite of seroconversion from hepatitis B surface antigen to antibody, hepatitis relapsed and serum alanine aminotransferase levels were persistently abnormal during the 3-year follow-up period. Liver biopsy performed 2 years after the onset of illness revealed chronic hepatitis. A retrospective review of the patient's serological test results revealed hepatitis C virus (HCV) RNA and the development of antibodies to HCV during the acute phase of illness as well as the persistence of HCV RNA during follow-up. Thus, we serologically and virologically proved that our patient had simultaneous acute infections with hepatitis B and C viruses and that these infections led to fulminant hepatic failure, relapse of hepatitis, and chronic hepatitis C.

Acute Disease↗
PubMed1995

Membrane staining for hepatitis B surface antigen on hepatocytes: a sensitive and specific marker of active viral replication in hepatitis B.

AIMS--To test the hypothesis that membranous staining of hepatitis B surface antigen (HBsAg) on the hepatocyte is a marker of active viral replication in chronic hepatitis B virus (HBV) infection. METHODS--Intrahepatic expression of HBsAg and hepatitis B core antigen (HBcAg) was studied by indirect immunofluorescence on frozen sections of liver specimens from 75 patients with chronic hepatitis B, and the results were correlated with serum levels of HBV-DNA assayed by spot hybridisation. RESULTS--Hepatocyte HBcAg was detected in all of 20 patients with serum levels of HBV-DNA > 1000 pg/ml, 18 (75%) of 24 patients with levels of HBV-DNA < or = 1000 pg/ml, and two (6.5%) of 31 patients without detectable serum HBV-DNA. The concordance between hepatocyte HBcAg and serum HBV-DNA was 89.3% (67/75). There were six patients (8%) who had detectable serum HBV-DNA but without hepatocyte HBcAg, and two patients (2.7%) who had detectable hepatocyte HBcAg but without serum HBV-DNA. Membranous staining of HBsAg associated with variable degrees of cytoplasmic HBsAg was found in all but one of 44 patients with serum HBV-DNA, irrespective of the levels, but in none of the 31 patients without serum HBV-DNA. Of the latter, HBsAg was distributed solely in the cytoplasm. In addition, there is an inverse correlation between serum levels of HBV-DNA and the degrees of cytoplasmic staining of HBsAg. The concordance between membranous staining fo HBsAg and serum HBV-DNA was 98.7% (74/75), significantly higher than that between hepatocyte HBcAG and serum HBV-DNA. CONCLUSIONS--Membranous staining of HBsAg on the hepatocyte correlated excellently with serum HBV-DNA and thus can be recognised as a sensitive and specific marker of active hepatitis B virus replication.

Adult↗
PubMed1995

Cellular immune responses in patients with dual infection of hepatitis B and C viruses: dominant role of hepatitis C virus.

Several lines of evidence have suggested that immune mechanisms are involved in the pathogenesis of hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related hepatitis. Study of patients with dual HBV and HCV infection raises the question of which is etiologically more relevant in determining the liver cell damage. To address this issue, proliferation of peripheral blood mononuclear cells (PBMCs) in response to a panel of HBV and HCV antigens was assayed in 13 patients with chronic dual hepatitis B and C, 7 patients with chronic hepatitis B, 7 patients with chronic hepatitis C, and 6 patients with hepatitis B surface antigen (HBsAg) carrier state. Although HBV or HCV hepatitis patients had a significant response to HBV or HCV antigens, respectively, the patients with dual hepatitis B and C exclusively responded to HCV antigens, but not to HBV antigens. One patients who was seropositive for both HBV-DNA and HCV-RNA showed a low response to HBV antigens initially but lost the response 3 months later and became responsive to more HCV antigens. These findings suggest that HCV has a dominant role in the immune response of the patients with dual HBV and HCV infection.

Adolescent↗
PubMed1995

T-cell--mediated autologous hepatocytotoxicity in patients with chronic hepatitis C virus infection.

Virus-specific cytotoxic T lymphocytes (CTLs) have been suggested to be responsible for the liver injuries in patients with hepatitis C virus (HCV) infection. However, there has been no report of direct evidence to substantiate this hypothesis. In this study, we performed in vitro autologous hepatocytotoxicity assay in 45 patients to examine a possible role of CTLs to HCV-infected live cells. The data were correlated with histology activity index of liver biopsy specimens. Lymphocyte subsets and hepatocyte expression of human major histocompatibility complex antigens class I and class II (HLA-I and HLA-II) were also evaluated. The immunohistochemical study showed more prominent HLA-I expression than HLA-II on hepatocytes (mean score +/- SEM:2.34 +/- 0.11 vs. 0.42 +/- 0.08; P < .01). The lymphocyte subset analysis showed that CD8+ T cells were dominant in the lobular areas showing spotty necrosis, whereas CD4+ T cells were prominent in the portal and periportal areas (P < .01). Most patients had a significant T cell-mediated cytotoxicity to hepatocytes as compared with non-T cells (percentage cytotoxicity +/- SEM:46.4 +/- 2.3 vs. 13.8 +/- 2.7; P < .001). T cell-mediated hepatocytotoxicity had a linear correlation with HAI (P < .05). The T cell-mediated cytotoxicity could be blocked by anti-CD8 (43.7% vs. 18.5%, P < .05) but not by anti-CD4 or anti-HLA-II monoclonal antibodies. These findings strongly suggest that HLA-I-restricted, CD8+ T cell-mediated hepatocytotoxicity is an important pathogenetic mechanism in patients with chronic HCV infection.

Adult↗
PubMed1995

First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen.

In the absence of a truly representative animal model, the question of whether EBV-related diseases can be prevented by a vaccine has been studied for the first time in humans. A live recombinant virus based on the licensed vaccinia strain Tien Tan, expressing under the 11K vaccinia promoter the major EBV membrane antigen BNLF-1 MA (gp 220-340), was constructed and tested in three different human populations: EBV-positive and vaccinia-virus-exposed adults; EBV-positive, non-vaccinia-virus-exposed juveniles; and EBV and vaccinia virus-naive infants. No significant titre variations for EBV were observed in the adults, but EBV-neutralising titres increased in the vaccinated juveniles, while antibodies to VCA of EBV remained unchanged. All nine vaccinated infants developed antibodies to MA (membrane antigen) with neutralising properties in vitro; three of these infants were infected by EBV via natural routes over a period of 16 months after vaccination and all ten unvaccinated control infants became infected. It has been shown for the first time that protection against and/or delay of EBV infection by the natural route is possible in humans and that live vaccinia vectors can be used and are efficacious.

Adult↗
PubMed1994

Role of the ribozyme of hepatitis delta virus on the transcription after polyadenylation.

We have previously demonstrated that the ribozyme located 34 nucleotides downstream of the polyadenylation site on the antigenomic RNA of the hepatitis delta virus can stabilize the downstream transcript after polyadenylation. Here, we have reports on further investigations of the molecular mechanism of this stabilization effect and the potential role of the small and large delta antigens. We found that the downstream transcripts after polyadenylation were stabilized by the ribozyme independently of either the small or large delta antigen. The stabilization effect was abolished as the ribozyme activity was eliminated by mutations on either the enzyme domain or target site of the ribozyme. These findings suggested that it was the ribozyme activity rather than the RNA structure or the delta antigens that contributed to the stabilization effect.

Base Sequence↗
PubMed1994

Alteration of the subcellular localization of hepatitis B virus core protein by large but not small surface proteins.

By performing immunofluorescence staining assays in confluent COS-7 cells, hepatitis B virus core, small surface and large surface proteins were found to localize largely in the nucleus, diffusely in the cytoplasm, and accumulatively in a perinuclear area, respectively. When two proteins were co-expressed, the core protein was found co-localized with the large but not small surface protein in the cytoplasm. By performing subcellular fractionation experiments, the large surface protein was found to reduce the amount of the core protein in the nuclear fraction to an undetectable level. These results indicate that the large but not small surface protein can alter the subcellular localization of the core protein.

Blotting, Western↗
PubMed1994

Polyadenylation of the mRNA of hepatitis delta virus is dependent on the structure of the nascent RNA and regulated by the small or large delta antigen.

During the hepatitis delta virus (HDV) RNA replication, synthesis of either the mRNA for the delta antigen (HDAg) or the full-length antigenomic RNA is determined by selective usage of the potent poly(A) signal on the antigenome. To elucidate the regulatory mechanism, HDV cDNA cotransfection system was used to examine the potential effect of the secondary structure of the nascent RNA and that of the HDAg on HDV polyadenylation in transfected cells. We found that when the nascent RNA species could fold itself to form the rodlike structure, the HDV polyadenylation was suppressed 3 to 5 fold by the HDAg. In addition, we observed that the small and the large HDAg exerted a similar suppressive effect on the HDV polyadenylation, though they played different roles in HDV replication. We concluded that the HDV polyadenylation could be regulated by the structure of the nascent antigenomic RNA and by either the small or large HDAg.

Antigens, Viral↗
PubMed1994

The role of hepatitis C virus in fulminant viral hepatitis in an area with endemic hepatitis A and B.

BACKGROUND/AIMS: The role of hepatitis C virus in fulminant hepatitis remains controversial and needs further investigation. The aim of this study was to examine the role of hepatitis C virus in fulminant hepatitis in an area with endemic hepatitis A and B. METHODS: Serological markers of hepatitis C virus were studied in 62 adults from Taiwan with fulminant viral hepatitis. RESULTS: Of 62 patients, 5 (8.1%) were infected with acute type B hepatitis, 11 (17.7%) were infected with acute non-A, non-B hepatitis, and the remaining 46 (74.2%) were hepatitis B surface antigen (HBsAg) positive but immunoglobulin M (IgM) antibody to hepatitis B core antigen negative. Of the latter, 11 (23.9%) were IgM antibody to hepatitis D virus positive, 16 (34.8%) had high-titered serum hepatitis B virus DNA (> 1000 pg/mL) and were suspected to have hepatitis B virus reactivation, and the other 19 (41.3%) had no identified causes. Serum hepatitis C virus RNA was found in 5 (45.5%) of 11 patients with fulminant non-A, non-B hepatitis, 3 (27.3%) of 11 HBsAg carriers with delta superinfection, and 6 (31.6%) of 19 HBsAg carriers with fulminant hepatitis of undetermined cause. CONCLUSIONS: Nearly half of fulminant non-A, non-B hepatitis and about 20% of HBsAg carriers with superimposed fulminant hepatitis in Taiwan could be attributed to hepatitis C virus infection.

Adult↗
PubMed1994

Displacement of hepatitis B virus by hepatitis C virus as the cause of continuing chronic hepatitis.

BACKGROUND/AIMS: It has been shown that hepatitis C virus (HCV) superinfection may suppress hepatitis B virus (HBV) leading to hepatitis B surface antigen (HBsAg) clearance and that hepatitis may persist after HBsAg clearance in a few patients. The role of HCV in continuing hepatitis after termination of chronic HBsAg antigenemia remains to be explored in a series of patients. METHODS: HCV markers were studied using second generation enzyme immunoassay and polymerase chain reaction with reverse transcription and were compared between 41 patients with persistent alanine aminotransferase (ALT) elevation (hepatitis group) and 82 age/sex-matched patients with normal ALT (control group) after HBsAg clearance. RESULTS: Twenty-six (63%) of the 41 hepatitis group patients were seropositive for antibodies to HCV (anti-HCV) compared with only 4 (5%) of 82 controls (P < 0.0001). Six patients of the hepatitis group and 1 control had an episode of acute hepatitis C with seroconversion of anti-HCV 1-68 months before HBsAg clearance. Of those seropositive for anti-HCV, serum HBV DNA was not detectable, and serum HCV RNA was detected in 23 (88.5%) of the 26 hepatitis patients but none of the 4 controls (P < 0.001). Liver biopsy in 6 anti-HCV positive patients with continuing hepatitis showed features compatible with chronic hepatitis C. HCV RNA, but not HBV DNA, was detected in liver tissues of these 6 patients. CONCLUSIONS: The results suggest that HCV may usurp the role of HBV in chronic hepatitis and act as the major cause of continuing hepatitis or ALT elevation after HBV/HBsAg clearance.

Adult↗
PubMed1994

Beneficial effect of prednisolone withdrawal followed by human lymphoblastoid interferon on the treatment of chronic type B hepatitis in Asians: a randomized controlled trial.

To evaluate the effect of interferon and the benefit of prednisolone pretreatment in Oriental patients with chronic active hepatitis B, 120 male Chinese patients were randomly allocated to receive: 1) group A: a 4-week course of prednisolone followed by 2 weeks of no treatment and then a 12-week course of human lymphoblastoid interferon, 4 to 6 MU/m2 intramuscularly; 2) group B: as group A, but with placebo given instead of prednisolone; 3) group C: an 18-week course of placebo. Clearance of serum hepatitis B virus-DNA and HBeAg (complete response) was achieved in 21% of group A, 5% of group B and none of group C at the end of therapy (A vs B: p = 0.054; A vs C: p < 0.01). When assessed 12 months after the end of therapy, the complete response rate was 46% in group A, 24% in group B and 25% in group C (p < 0.05). Those with baseline alanine transaminase < or = 200 U/l showed a better response to interferon following prednisolone withdrawal (48%) than with interferon therapy alone (20%, p = 0.056) and no treatment (9%, p < 0.01). Those with a baseline serum hepatitis B virus-DNA < or = 1000 pg/ml also showed a higher complete response rate when pretreated with prednisolone (59%) than when treated with interferon alone (29%, p = 0.084) or untreated (22%, p < 0.03). The strongest independent predictor of a response to treatment was prednisolone withdrawal (p < 0.05). None of the responders lost hepatitis B surface antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Role of hepatitis C and delta viruses in the termination of chronic hepatitis B surface antigen carrier state: a multivariate analysis in a longitudinal follow-up study.

Influences of hepatitis delta (HDV) or C virus (HCV) superinfection on the spontaneous clearance of hepatitis B virus (HBV) surface antigen (HBsAg) were investigated in 992 patients. Patients were infected with HBV alone (group 1), HBV and HDV (group 2), HBV and HCV (group 3), or all three viruses (group 4). They were followed for 6.2 +/- 3.7 years. Thirty-six patients (3.6%) had spontaneous serum HBsAg clearance. There was an increasing linear trend in the annual incidence from 0.43% (group 1) to 0.64% (group 2), 2.08% (group 3), and 2.33% (group 4; P < .0001). Relative risk (RR) of group 3 to 1 was 4.8 (P < .001) and of group 4 to 1 was 5.1 (P < .02). RR was significantly higher in group 3 than 2 (P < .02). By Cox multivariate regression analysis, only HCV superinfection and age at entry were significant influencing factors. Moreover, there was a significant interaction between HCV and age. Patients > 35 years old with HCV had a higher HBsAg clearance rate. Results suggest that HCV is the most important hepatotropic virus that enhances HBsAg clearance in chronic hepatitis B.

Adolescent↗
PubMed1994

Absence of precore stop mutant in chronic dual (B and C) and triple (B, C, and D) hepatitis virus infection.

Sequences of hepatitis B virus (HBV) precore regions from 7 patients with HBV and hepatitis C virus (HCV) dual infection and 2 with HBV, HCV, and hepatitis D virus (HDV) triple infection were analyzed. Two patients, 1 with only acute HBV infection and 1 with only chronic HBV infection, were also included for comparison. All patients had antibodies against HBV e antigen (anti-HBe) except 1 with chronic hepatitis B and C. No precore stop mutation at codon 28 (TGG to TAG mutation) was found in 21 cloned sequences from the 7 patients with HBV and HCV infection, nor in 11 cloned sequences from 2 patients with HBV, HCV, and HDV infection. However, mutations in other positions of the precore region were observed in 2 patients with hepatitis B and C. In both cases, precore sequences with mutations in different positions were obtained from the same serum sample. No mutations were observed in other positions of the precore region in the 2 patients with hepatitis B, C, and D. The presence of anti-HBe in these patients was probably due to the low level of HBV replication and not to the presence of the precore stop mutant.

Adult↗
PubMed1994

Early detection of anti-HCc antibody in acute hepatitis C virus (HCV) by western blot (immunoblot) using a recombinant HCV core protein fragment.

Crude extract from Escherichia coli which expressed a recombinant protein containing amino acids 2 to 127 of the hepatitis C virus (HCV) core protein was used to detect the antibody against HCV core protein (anti-HCc). After electrophoretic separation of proteins from the extract, Western blot (immunoblot) analysis was performed with the serum samples. This method was compared with a commercially available second-generation enzyme immunoassay (EIA) which employed synthetic peptides corresponding to highly antigenic segments of both structural and nonstructural portions of HCV. Also, reverse transcription PCR for HCV RNA was used for comparison. Seventy-two serum samples from three groups of patients were tested. Groups I and II represented healthy subjects and subjects with acute hepatitis A or B, respectively. Group III included patients with newly acquired acute hepatitis C. By Western blot analysis, 31 of 31 (100%) samples from group I were negative for anti-HCc antibody, whereas 4 of 22 (18%) samples from group II were positive for anti-HCc. One of these four samples was also positive for anti-HCV antibody by the second-generation EIA (1 of 22 [4.5%]). Among 19 patients diagnosed with newly acquired acute hepatitis C, 4 (21%) were positive for anti-HCV by the second-generation EIA, whereas 12 of 19 (63%) were positive for anti-HCc by Western blot analysis. Of EIA-positive subjects, 4 of 4 (100%) were also positive for anti-HCc by Western blot analysis, whereas among EIA-negative subjects, 8 of 15 (53%) were positive. For HCV RNA detected by reverse transcription PCR, 15 of 19 (80%) of this group of samples were positive. Strikingly, the peak bilirubin level for patients with EIA-negative and Western blot-positive results is significantly higher than that for patients with consistent EIA and Western blot results (22.7 versus 7.2 mg/dl). A series of serum samples from a patient with concurrent hepatitis B and C viral infection was also studied by both tests. Although anti-HCc persisted throughout the course of infection, anti-HCV by EIA converted from negative to positive 20 days after admission and then converted back to negative 30 days later.

Acute Disease↗
PubMed1993

Sex difference in chronic hepatitis B virus infection: studies of serum HBeAg and alanine aminotransferase levels in 10,431 asymptomatic Chinese HBsAg carriers.

To study the difference between the sexes with regard to chronic hepatitis B virus infection, we surveyed levels of serum hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) among 10,431 asymptomatic Chinese carriers of hepatitis B surface antigen (HBsAg) in Taiwan. There were 7,095 men and 3,336 women in this study; ages ranged from 15 to 70 years. HBeAg was detected in 19.6% of HBsAg carriers. The prevalence of HBeAg decreased significantly with increasing age. HBeAg was detected in 17.7% of men and 23.6% of women. After correction for the confounding effect of age, it was found that the prevalence of HBeAg was significantly higher among women than among men. The level of serum ALT was abnormal in 20.8% of HBsAg carriers. Abnormal ALT levels were significantly more frequent among HBsAg carriers who tested positive for HBeAg (39.7%) than among those who did not (16.2%; P < .001). Among the HBeAg-positive carriers, 43.2% of men and 34.2% of women had abnormal ALT levels, and men were 1.45 times more likely to have abnormal ALT levels than women (P < .001). Among the carriers who were negative for HBeAg, 20.6% of men and only 6.0% of women had abnormal ALT levels, and men were 3.98 times more likely to have abnormal ALT levels than women (P < .001). Overall, 24.6% of men and only 12.6% of women had abnormal ALT levels, and men were 2.33 times more likely to have abnormal ALT levels than were women (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effects of prednisolone pretreatment in interferon alfa therapy for patients with chronic non-A, non-B (C) hepatitis.

The effect of corticosteroid pretreatment on interferon alfa treatment of chronic non-A, non-B or C hepatitis was evaluated in an open, randomized, controlled study. Normalization of the serum alanine aminotransferase level, which suggested complete response, was recorded in 14 (56%) of 25 patients at the end of a 6-month treatment with 3 million units of interferon alfa three times weekly alone. Prednisolone withdrawal followed by the same interferon alfa treatment resulted in complete response in 14 (61%) of another 23 patients. Both of these rates are significantly higher than the spontaneous ALT normalization rate of 9% observed in 2 of 22 patients during the same period (p < 0.01). ALT normalized within 2 months of interferon therapy in most (89%) of the complete responders. Of the patients pretreated with prednisolone, 43% showed a "rebound" following prednisolone withdrawal and 89% of the patients with "rebound" responded to subsequent interferon therapy. The cumulative probability of sustained remission in patients with and without prednisolone pretreatment in a 24-month period of follow-up after the end of therapy was 79% and 30%, respectively (p < 0.05). Clinical relapse mostly (85%) occurred within 3 months after the end of therapy. No obvious factor could be identified as a predictor of response or relapse. The results of this study suggest that prednisolone withdrawal tends to enhance the durability of the beneficial effects of interferon alfa therapy in patients with chronic non-A, non-B or C hepatitis.

Alanine Transaminase↗
PubMed1993

Coexpression of intercellular adhesion molecule-1 and class I major histocompatibility complex antigens on hepatocyte membrane in chronic viral hepatitis.

AIMS: To evaluate the role of hepatocyte expression of leucocyte adhesion molecules and major histocompatibility complex (MHC) antigens in the pathogenesis of chronic viral hepatitis. METHODS: The expression of intercellular adhesion molecule 1 (ICAM-1), lymphocyte function associated antigen 3 (LFA-3), and MHC class I and II antigens on hepatocyte membrane in relation to the histological and biochemical activities was studied in patients with chronic B hepatitis, chronic persistent hepatitis (CPH) n = 23; chronic active hepatitis (CAH) n = 20; chronic D hepatitis (CAH) n = 6; and chronic non-A, non-B hepatitis (CPH n = 4, CAM n = 6). Six of the latter were hepatitis C virus antibody positive. RESULTS: In chronic B hepatitis ICAM-1 and MHC-I were expressed significantly more in patients with CAH than in those with CPH (p < 0.001), while the expression of LFA-3 and MHC-II showed no significant difference, irrespective of serum HBeAg or hepatitis B virus DNA. Similar findings were noted in non-A, non-B hepatitis. Regardless of the viral aetiology, patients with CAH had a significantly higher degree of ICAM-1 and MHC-I expression than LFA-3 (p < 0.001 v ICAM-1 and MHC-I, respectively) and MHC-II (p < 0.001 v ICAM-1 and MHC-I, respectively) expression. Those with CPH showed little or no difference in the expression of these four molecules. Furthermore, serum ALT values positively correlated with the hepatocyte expression of ICAM-1 (p < 0.001) and MHC-I (p < 0.001), but not LFA-3 (p > 0.05) and MHC-II (p > 0.05). CONCLUSIONS: In chronic viral hepatitis hepatocyte expression of ICAM-1 and MHC-I might be important for immunosurveillance against virally infected hepatocytes, while the expression of LFA-3 and MHC-II does not seem to have a role in the pathogenesis of chronic viral hepatitis.

Antigens, CD↗