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Biomedical subjects

I S Sheen

Publications and source records attributed to I S Sheen.

At least 55 records · Page 3Linked to original sources

Serum carboxy terminal propeptide of type I procollagen to amino terminal propeptide of type III procollagen ratio is a better indicator than each single propeptide and 7S domain type IV collagen for progressive fibrogenesis in chronic viral liver diseases.

Twenty chronic viral hepatitis patients, mainly with hepatitis B related with progression to liver cirrhosis were included for an assay of serum collagen markers: PICP (carboxy terminal propeptide of type I procollagen), PIIINP (amino terminal propeptide of type III procollagen), and 7S-IV (7S-domain type IV collagen). PICP is increased in 20% of chronic hepatitis patients with a mean of 190.3 ng/ml, which is not different from that of the follow-up concentration in liver cirrhosis, where 35% of cases were abnormal with a mean of 220.5 ng/ml. The serum level and percent of abnormality of PIIICP in chronic hepatitis and in liver cirrhosis are 23.5 ng/ml vs 14.8 ng/ml and 90% vs 100%, respectively (P > 0.05). PICP/PIIINP is significantly higher during liver cirrhosis (15.11 vs 10.08, P < 0.05). PICP during chronic hepatitis is not related to serum biochemical changes, while PICP during liver cirrhosis and PIIINP are correlated with hepatic enzymes. 7S-IV in chronic hepatitis and in liver cirrhosis is 14.0 ng/ml vs 10.9 ng/ml, respectively; both were positively correlated with hepatic enzymes. These results suggest that PICP/PIIINP is a better indicator of hepatic fibrogenesis than either PICP or PIIINP alone in viral hepatitis. A ratio of more than 12 is suggestive of liver cirrhosis.

Adult↗

Serum levels of interferon-alpha and -gamma in acute and chronic hepatitis B virus infection.

To evaluate the potential implication of in vivo interferon production in the pathogenesis of different forms of acute and chronic hepatitis B virus infection, serum levels of interferon-alpha and -gamma were measured using immunoassay techniques in 20 patients with acute hepatitis B who subsequently cleared the virus (group Ia), 8 patients with acute hepatitis B who became HBsAg carriers (group Ib), 55 patients with chronic hepatitis B (group II), and 15 healthy controls. None of the controls had interferon-alpha or -gamma detectable in serum, while 15% and 100% of group Ia patients, 25% and 100% of group Ib patients, and 22% and 15% of group II patients, had raised serum levels of interferon-alpha and -gamma, respectively. Serum interferon-gamma was detected significantly more frequently in group Ia and Ib patients than in controls and in group II patients. Among patients with acute hepatitis B, serum levels of interferon-alpha and -gamma showed no significant difference between group Ia and group Ib patients. Among patients with chronic hepatitis B, interferon-alpha was detected significantly more frequently in patients with serum HBV-DNA (31.4% or 11/35) than in those without (5% or 1/20), whereas interferon-gamma was detected significantly more frequently in patients with chronic active hepatitis (28% or 7/25) than in those with chronic persistent hepatitis (3.3% or 1/30). In conclusion, in acute hepatitis B, serum levels of interferon-alpha and -gamma did not show a significant difference between patients who subsequently cleared the virus and those who became HBsAg carriers.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Subcellular localization of hepatitis B core antigen in relation to hepatocyte regeneration in chronic hepatitis B.

BACKGROUND & AIMS: To test whether the dominant cytoplasmic expression of hepatitis B core antigen (HBcAg) in active chronic hepatitis B is secondary to liver damage and regeneration, the relationship between subcellular localization of HBcAg, liver inflammatory activity, and hepatocyte regeneration in chronic hepatitis B was studied. METHODS: Correlation of the clinical and laboratory data with the topographical distribution of HBcAg was studied in 30 patients. The subcellular localization of HBcAg in relation to hepatocyte cell cycles was studied by double immunostaining of HBcAg and proliferating cell nuclear antigen. RESULTS: Patients with predominant cytoplasmic HBcAg had significantly higher levels of biochemical and histological activities and proliferating cell nuclear antigen expression than patients with predominant nuclear HBcAg. The levels of proliferating cell nuclear antigen expression correlated positively with biochemical and histological activities and degrees of cytoplasmic HBcAg expression but negatively with degrees of nuclear HbcAg expression. Proliferating cell nuclear antigen expression was shown in 49% of hepatocytes with cytoplasmic HBcAg but in only 2% of hepatocytes with nuclear HBcAg. CONCLUSIONS: These findings suggested that, following liver damage, the regeneration of surviving hepatocytes might cause the shift of intracellular HBcAg from nucleus to cytoplasm. As a result, the extent of nuclear HBcAg expression reduces with concomitant increase in cytoplasmic HBcAg expression.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

Vibrio vulnificus infection--report of 8 cases and review of cases in Taiwan.

Vibrio vulnificus infection, which is a rare and fatal disease, can be categorized clinically as either primary septicemia or wound infection. The clinical presentation of patients with primary septicemia can vary from fever alone to a more severe illness including high-grade bullous lesions, hypotension, and shock. Wound infection typically results from either injury to the skin in a marine environment or contact of a preexisting wound with sea water. We reported eight cases with Vibrio vulnificus infection in Chang gung Memorial Hospital and reviewed ten other cases previously reported with details in Taiwan. Fourteen patients presented with primary septicemia, and four with wound infection. Thirteen patients had alcoholism or chronic liver disease, two had peptic ulcer disease, one was steroids abuser, and one patient had thalassemia and chronic liver disease. Overall mortality was 55.6% (ten patients). Patients with hypotension within 48 hours of admission had higher mortality than normotensive patients (77% vs. 0%, P = 0.007). Patients with chronic liver disease or liver cirrhosis also had tendency to a higher mortality than not (64% vs. 25%, P = 0.274). Chronic liver diseases and liver cirrhosis are common disease in Taiwan. They take a high risk for Vibrio vulnificus infection. Clinician should keep in mind of this potentially fatal infection in these patients reporting a history of recent raw oyster consumption and presented with sepsis and characterized skin lesions. Prompt empirical antibiotics treatment and aggressive surgical treatment may be lifesaving for this acute and fatal disease.

Adult↗

Ultrasonographic changes of early liver cirrhosis in chronic hepatitis B: a longitudinal study.

Ultrasonography of prospectively followed chronic hepatitis B patients who developed liver cirrhosis were reevaluated in order to identify the ultrasonographic changes of early cirrhosis. Ultrasonographic features of 29 patients before and after cirrhosis were as follows: portal vein diameter--1.20 cm/1.29 cm (NS); cirrhosis score--5.69/7.52 (p < 0.01); spleen size index--21.99 cm2/25.84 cm2 (NS). The result suggests that ultrasonographic diagnosis of early cirrhosis is not easy on a single occasion; however, the score system method is helpful in longitudinal follow-up chronic hepatitis patients. A careful comparison of hepatic parenchymal and surface changes are mandatory.

Chronic Disease↗

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↗

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↗

Eosinophilic gastroenteritis: 10 years experience.

Eight patients (five men, three women), mean age 36.9 +/- 13.5 (17-60) yr, were diagnosed to have eosinophilic gastroenteritis. The condition was proved in five patients by biopsies through endoscope, and in three, by operation. All had hypereosinophilia (absolute eosinophil count of 1,337-21,787/cm3). According to Klein classification, two had mucosal disease, three had muscle layer disease, and three, subserosal disease. The most common symptoms were abdominal pain (100%), diarrhea (62.5%), vomiting (62.5%), and nausea (50%). Four patients (50%) had symptoms for more than 1 yr before diagnosis. Barium studies revealed mucosal edema and/or thickening of the small intestinal wall in three cases (including one case with ulceration), partial gastric outlet obstruction in one case, and narrowing of lumen of the terminal ileum in one case. Hypotonic duodenogram revealed double contour in one case. Ultrasound examination revealed thickening of the intestinal wall in two cases; computer tomography revealed thickening of the intestinal wall in one case. All patients were treated with steroid (40 mg/day for initial dose and relapse; 5-10 mg/day for maintenance). The symptoms subsided and the eosinophil counts returned to normal within 2 wk in seven patients and 1 month in one. Of six patients being followed up for 2-10 yr, one had remission, four needed small maintenance dose of steroid, and one suffered from relapse with intestinal perforation.

Adolescent↗

Concurrent hepatitis C virus and hepatitis delta virus superinfection in patients with chronic hepatitis B virus infection.

Since hepatitis C virus (HCV) and hepatitis delta virus (HDV) are transmitted by the same routes as hepatitis B virus (HBV), simultaneous or concurrent HCV and HDV infection in patients with chronic HBV infection may occur. To test this hypothesis and to examine the clinicohistological and immunopathological presentations of such multiple hepatitis virus infections, acute and/or convalescent serum specimens from 86 patients with acute HDV superinfection were tested by enzyme immunoassay for antibodies to HCV. Of the 86 patients, 18 (20.9%) were associated with HCV infection. Although patients with early mortality cannot be evaluated by the HCV markers used in this study, the results showed that the clinical and histologic features were similar except that patients with HCV infection were older than those without HCV infection (P less than 0.01). Immunopathological studies carried out within 2 months after the onset of acute HDV superinfection demonstrated that hepatitis B core antigen (HBcAg) was not detected in any patient and HDV antigen was detected in 18.2% of the patients with HCV infection whereas HBcAg and HDAg were found in 7% and 65.1%, respectively, of those without HCV coinfection (P less than 0.02). It is concluded that concurrent HCV and HDV superinfections can and do occur in patients with chronic HBV infection. In these triple viral infections, HCV may even transiently suppress HDV and HBV.

Adult↗

Hepatitis C virus in peripheral blood mononuclear cells.

RNA extracted from plasma and peripheral blood mononuclear cells of patients with chronic hepatitis C were used as the template for reverse transcription followed by double in vitro enzymatic amplification with nested primers. Hepatitis C virus was detected in 14 of 15 (93.3%) plasma specimens and in 8 of 15 (53.3%) peripheral blood mononuclear cell specimens obtained from patients with chronic hepatitis C and abnormal liver functions. The results suggest that hepatitis C virus could be found frequently in peripheral blood mononuclear cells of patients with chronic hepatitis C. Whether the presence of hepatitis C virus in peripheral blood mononuclear cells plays any role in the pathogenesis of diseases associated with hepatitis C virus infection remains to be determined.

Base Sequence↗