Biomedical subjects

I S Sheen

Publications and source records attributed to I S Sheen.

At least 19 recordsLinked to original sources

PubMed1998

Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial.

Thymosin alpha1 (Talpha) is an immune modifier that has been shown in a pilot study to be effective for chronic hepatitis B; this requires confirmation. Ninety-eight patients with clinicopathologically proven chronic hepatitis B were randomly allocated to 3 groups: 1) group A received a 26-week course of Talpha with a 1.6-mg subcutaneous injection two times a week (T6 group); 2) group B received the same regimen as group A, but Talpha therapy extended for 52 weeks (T12 group); and 3) group C served as a control group and was followed up for 18 months without specific treatment (T0 group). The three groups were comparable in clinicohistological features at entry. The complete virological response rate (clearance of serum hepatitis B virus [HBV] DNA and hepatitis B e antigen [HBeAg]) was higher in group A (40.6%) and group B (26.5%) than in group C (9.4%) (group A vs. group C: P=.004; group B vs. group C: P=.068) when assessed 18 months after entry, although complete response rates among these three groups were similar when first assessed at the end of therapy. There was a trend for complete virological response to increase or accumulate gradually after the end of Talpha therapy. None of the responders lost hepatitis B surface antigen. Blinded histological assessment showed a significant improvement in treated patients, particularly in lobular necroinflammation and scores excluding fibrosis. No significant side effects were observed. These results suggest that a 26-week course of Talpha therapy is effective and safe in patients with chronic hepatitis B.

Adolescent↗

PubMed1998

Clinical and virological course of chronic hepatitis B virus infection with hepatitis C and D virus markers.

OBJECTIVE: Hepatitis B, C, and delta virus (HBV, HCV, HDV) share similar transmission routes; thus, dual or triple infections may occur and even persist in the same patient. However, little is known about the presentations and course of chronic HBV infection with HCV and HDV markers, which this study examined. METHODS: Antibodies against HCV (anti-HCV) and HDV (anti-HDV) were assayed as appropriate in patients with HBV infection. The clinical, pathological, and virological presentations as well as the course of the disease in patients with HBV/HDV/HCV triple infection markers were then reviewed. RESULTS: A total of 60 patients, 51 men and nine women, age 19-67 yr (mean 45.9+/-1.6 yr) were identified. Of these 60 patients, five (8.3%) were HBeAg positive and 10 (16.7%) cirrhotic at entry, 30 (50%) presented with acute superinfection (HCV or HDV, or both) and the remaining 30 presented with chronic liver disease. On presentation, 16 (53.3%) of the 30 patients with acute superinfection showed hepatic decompensation and eight (26.7%) died. In contrast, only one of the patients with "chronic liver disease" presented with hepatic decompensation. Of the 42 patients followed up for 1-15 (mean, 4.7+/-0.6) yr, 45.2% showed remission and 19% showed HBsAg seroclearance, whereas 12.5% of the 32 noncirrhotics developed cirrhosis and three of the nine cirrhotics became decompensated. At the end of follow-up, 29 patients (69.9%) were still seropositive for HCV-RNA but only nine (22.5%) were seropositive for HDV-RNA and five (12.5%) were seropositive for HBV-DNA. CONCLUSIONS: These results suggest that infection with HBV, HCV, and HDV triple markers is a severe disease in acute superinfection stage but that the course is relatively benign, slowly progressive, and usually dominated by HCV.

Adult↗

PubMed1997

Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers.

The authors conducted a study to assess the importance of underlying liver cirrhosis in the development of hepatocellular carcinoma (HCC) and the multifactorial etiology of liver cirrhosis in chronic carriers of hepatitis B virus (HBV). Between November 1980 and May 1990, all male hepatitis B surface antigen (HBsAg) carriers who routinely attended a clinic for asymptomatic HBV carriers at the Liver Unit of Chang-Gung Memorial Hospital, Taiwan, were enrolled in the study (n = 1,506). The authors used this cohort to investigate prospectively for liver cirrhosis and HCC at 6-month intervals by means of ultrasonography and clinical assessment. There were 16 incident cases of HCC and 89 cases of liver cirrhosis (78 of whom were detected during follow-up) identified after an average follow-up of 7.1 years. Subclinical liver cirrhosis diagnosed by ultrasonography was significantly associated with the risk for HCC (multivariate-adjusted relative risk (RR) = 11.8, 95% confidence interval (CI) 3.9-35.8). By multivariate analysis, the significant risk factors found for liver cirrhosis in HBsAg carriers were age, hepatitis B e antigen (HBeAg) carrier status, chronic hepatitis manifested by sustained elevated serum aminotransferase levels for > or = 6 months, cigarette smoking, non-A blood types, and low educational levels. Habitual alcohol drinking was not independently related to liver cirrhosis. However, the risk of liver cirrhosis associated with smoking was more striking among drinkers than nondrinkers (> or = 20 cigarettes/day vs. nonsmokers: drinkers, RR = 9.3, 95% CI 1.1-78.8; nondrinkers, RR = 1.85, 95% CI 0.98-3.51), which suggests a possible modification effect of alcohol drinking on the liver cirrhosis risk of cigarette smoking. The authors observed synergistic effects on liver cirrhosis development for cigarette smoking with HBeAg carrier status and chronic hepatitis.

Adult↗

PubMed1997

Quantitative assessment of hepatitis C virus RNA by polymerase chain reaction and a digoxigenin detection system: comparison with branched DNA assay.

A method for quantifying hepatitis C virus (HCV) RNA in serum using reverse transcription-polymerase chain reaction (RT-PCR) followed by slot-blot hybridization with a specific, digoxigenin-labeled probe was developed. Using RNA synthesized from cloned HCV cDNA as a standard, serum concentration of HCV RNA above 10 copies/ml can be quantitatively determined. To compare this method with branched DNA (bDNA) assay, 45 serum samples from 26 patients with newly acquired acute hepatitis C (n = 16) or hepatitis C with acute exacerbation (n = 10) were submitted to both assays. HCV RNA in 30 (67%), 12 (27%) and three (6.7%) samples can be quantitatively determined by both, either and none of the two assays, respectively. Using a standardized qualitative HCV RNA detection test (Amplicor HCV test) as a reference, 1 and 0 false positive results were found by bDNA and this assay, respectively. This quantitative assay using RT-PCR and a digoxigenin detection system was comparable to bDNA assay. Since a false positive result was rarely found, this technique can be used as a first line test to screen a large number of samples rapidly and economically.

Acute Disease↗

PubMed1997

Response of patients with dual hepatitis B virus and C virus infection to interferon therapy.

Patients with dual infection with hepatitis B virus (HBV) and delta virus (HDV) responded poorly to interferon (IFN) therapy. Little is known about the effect of IFN therapy in patients with HBV and hepatitis C virus (HCV) dual infection. The patients in two randomized controlled trials with chronic HBV infection were retrospectively assayed for HCV markers. The HBV responses to IFN therapy in patients with and without HCV markers were compared. An open trial was conducted in 4 patients who had lost their serum HBV surface antigen (HBsAg) but had continuing HCV viremia and hepatitis. Of the 15 patients seropositive for HCV marker(s), only 1 (6.7%) responded with seroclearance of HBV DNA and HBV e antigen, as compared with 46 (28%) of 164 HCV-negative patients (p = 0.058). Icteric hepatitis developed in 1 patient on emergence of serum HCV RNA in association with seroclearance of HBV DNA. In contrast, good response was demonstrated in 3 of the 4 patients who had lost serum HBsAg before therapy. The results suggest that IFN therapy is not only of limited value in patients with dual infection with HBV and HCV but also has a potential risk of severe hepatitis if the clearance of one virus removes its suppressive effect on and facilitates the emergence of the other. However, patients with continuing HCV hepatitis after termination of the chronic HBsAg carrier state responded well to IFN therapy.

Adult↗

PubMed1997

The degrees of hepatocyte nuclear but not cytoplasmic expression of hepatitis B core antigen reflect the level of viral replication in chronic hepatitis B virus infection.

Although immunodetection of hepatitis B core antigen (HBcAg) in the liver has long been recognized as a marker of active hepatitis B virus (HBV) replication, the correlation between the level of viral replication and the degrees of expression of HBcAg in hepatocytes remains to be established. In this study, we examined the semiquantitative relationship between the level of HBV DNA in serum and the degree of expression of HBcAg in the hepatocyte nucleus or cytoplasm in 80 adults with chronic hepatitis B. Expression of HBcAg in hepatocytes was studied by the avidin-biotin immunoperoxidase method, and the results were scored on a scale of 0 to 4, values corresponding to the positivity of 0, 1 to 10, 11 to 25, 26 to 50, and > 50%, respectively, of hepatocytes examined. Serum HBV DNA was tested by a liquid hybridization assay, and the results were scored on a scale of 0 to 5, values corresponding to undetectable levels and levels of < or = 50, 51 to 100, 101 to 150, 151 to 200, and > 200 pg/ml, respectively. The results revealed a highly significant, positive correlation between the level of HBV DNA in serum and the degree of expression of HBcAg in nuclei (Spearman rank correlation coefficient [rs] = 0.653, P < 0.001). The mean scores (95% confidence intervals) of levels of HBV DNA in sera of patients whose levels of expression of HBcAg in nuclei received a score of 0 (n = 33), 1 or 2 (n = 35), and 3 or 4 (n = 12) were 1.3 (1.1 to 1.5), 2.5 (2.1 to 2.9), and 3.9 (3.1 to 4.7), respectively. However, no correlation between the level of HBV DNA in serum and the degree of expression of HBcAg in the cytoplasm was noted (rs = 0.026, P > 0.8). In conclusion, the degree of expression of HBcAg in the hepatocyte nucleus but not the cytoplasm can accurately reflect the level of viral replication in patients with chronic hepatitis B.

Adult↗

PubMed1996

Acute exacerbations in chronic hepatitis C: a clinicopathological and prognostic study.

BACKGROUND/METHODS: To examine the incidence, predisposing factors, clinicopathological characteristics and implications of acute exacerbations in chronic hepatitis C, a consecutive series of 194 biopsy-verified, anti-HCV-positive and hepatitis B surface antigen-negative patients were followed up and studied for the events of acute exacerbations, sustained biochemical resolution and development of cirrhosis. RESULTS: During a mean period of 6.2 +/- 3.5 (1.0-14.0) years, 151 episodes of acute exacerbations were recorded in 78 patients (40.2%). The estimated annual incidence of acute exacerbations was 11.9%. Fifty-five percent of acute exacerbations were asymptomatic. Histological study of acute exacerbations showed mild to moderate lobular inflammatory activities without bridging hepatic necrosis in all and periportal piecemeal in 23 (42.6%). The clinicopathological features of acute exacerbations in patients with chronic hepatitis C were less severe than those in patients with chronic hepatitis B. The route of infection, sex, age, mode of clinical presentation and the initial histology did not influence the occurrence of acute exacerbations. Only those with alanine aminotransferase > or = 300 U/l at entry tended to develop acute exacerbations more frequently (p < 0.001, odds ratio = 3.6, 95% confidence interval: 1.9-6.5). Acute exacerbations per se did not influence the subsequent development of cirrhosis or sustained biochemical resolution. Cirrhosis developed more frequently in patients with chronic active hepatitis at entry (p < 0.001, odds ratio = 6.5, 95% confidence interval: 2.6-16.0). Compared with baseline HCV-RNA level, HCV-RNA increased in 61% of acute exacerbations but the genotype remained unchanged in 75%. CONCLUSIONS: These results suggest that acute exacerbations also occur frequently in patients with chronic hepatitis C. They are clinically indolent, histologically less severe and not likely to be followed by sustained remission or development of cirrhosis.

Adult↗

PubMed1996

A prospective randomized trial of colchicine in prevention of liver cirrhosis in chronic hepatitis B patients.

BACKGROUND: The clinical course of chronic hepatitis B is variable. Patients with hepatic decompensation, bridging necrosis or an alpha-fetoprotein level greater than 100 ng/mL during an exacerbation of hepatitis have a high risk of developing cirrhosis. This study was conducted to evaluate the effect of colchicine in the prevention of cirrhosis in such patients. METHODS: Patients with risk factor(s) were randomized to receive either colchicine 5 mg/week or no specific treatment, the end point being development of cirrhosis. RESULTS: After a follow up period of 4 years, the treatment group had a marked reduction in exacerbations of acute hepatitis (32% vs. 63%/patient/year, P < 0.005). Seven out of 38 patients in the treatment group and 10 out of 27 patients in the control group developed cirrhosis. The calculated cumulative incidence of cirrhosis by the end of first, second, third and fourth years in the treatment group was 8.7, 18.6, 32 and 32%, respectively. The corresponding figures in the control group were 30, 35.5, 46.3 and 73.2%, respectively, with a P-value of 0.057. CONCLUSIONS: The results suggest that colchicine may prevent cirrhosis in chronic hepatitis B patients with risk factor(s), possibly by suppressing exacerbations of hepatitis through an anti-inflammatory effect.

Adult↗

PubMed1996

Severe clinical rebound upon withdrawal of corticosteroid before interferon therapy: incidence and risk factors.

To analyse the incidence and risk factors of clinical rebound and hepatic decompensation during or upon withdrawal of prednisolone pretreatment before interferon (IFN) therapy, two series of Taiwanese patients with chronic viral hepatitis from two independent randomized controlled trails were compared. Group 1 included 41 patients with chronic hepatitis B who were pretreated with daily prednisolone (30 mg) for 3 weeks, 15 mg for 1 week and no prednisolone for 2 weeks prior to lymphoblastoid IFN therapy. Group 2 consisted of 59 patients with chronic hepatitis B who were pretreated with daily prednisolone (40 mg) for 2 weeks, 30 mg prednisolone for 2 weeks, 20 mg prednisolone for 2 weeks and no prednisolone for 2 weeks prior to INF alpha-2a therapy. Clinical rebound developed more frequently in group 2 (67.8%) than in group 1 patients (41.5%; P < 0.01). The peak serum transaminase levels of group 1 and 2 patients during clinical rebound were similar. Icteric and symptomatic clinical rebound occurred in four (one cirrhotic) group 2 patients. The incidence of hepatic decompensation was 3.4% in group 2 patients, or 5.0% in group 2 patients with clinical rebound. Patients pretreated with a higher dose (40 mg) of prednisolone (odds ratio 3.0; 95% CI 1.3-6.6; P < 0.01) and non-cirrhotic patients (odds ratio 6.2; 95% CI 1.2-32.1; P < 0.02) tended to suffer from clinical rebound more frequently. However, once clinical rebound develops in cirrhotic patients, the relative risk of decompensation is 16 times that of non-cirrhotic patients. These results suggest that clinicians should be cautious in prescribing a short course of corticosteroids for patients with chronic viral hepatitis, because hepatic decompensation might occur in Oriental people with or without cirrhosis.

Adult↗

PubMed1996

Precore mutant of hepatitis B virus prevails in acute and chronic infections in an area in which hepatitis B is endemic.

By using an amplification-created restriction site method, the precore TAG mutant of hepatitis B virus was detected in 6 (75%) of 8 acute fulminant hepatitis B patients, 7 (58%) of 12 acute self-limiting hepatitis B patients, 35 (81%) of 43 hepatitis B virus surface antigen carriers with fulminant hepatitis, and 42 (70%) of 60 hepatitis B virus surface antigen carriers with chronic hepatitis. The precore TAG mutant prevails in acute and chronic hepatitis B of various severity in this area where hepatitis B is endemic.

Acute Disease↗

PubMed1996

Non-O1 Vibrio cholerae bacteremia in patients with cirrhosis: 5-yr experience from a single medical center.

OBJECTIVES: To assess the clinical features and susceptibility of cirrhotic patients to non-O1 Vibrio cholerae bacteremia and to provide our therapeutic experiences in this rare and high lethal infection. METHODS: Twenty-eight blood culture isolates of non-O1 V. cholerae were identified by our clinical microbiology laboratory between July 1989 and June 1994. Patients with underlying cirrhosis and the aforementioned bacteremia were retrospectively reviewed. RESULTS: Twenty-one cirrhotic patients (16 male, five female; mean age, 50.9 yr; range 28-67 yr) were identified and classified as Child B (6 cases) and Child C (15 cases). Bacteremic episodes occurred most often from March to September. Seafood ingestion (seven cases) and seawater exposure (two cases) were risk factors, but nosocomial infections were also noted in six cases. Presenting symptoms and signs included ascites (95.2%), fever (81%), abdominal pain (52.4%), diarrhea (33.3%), and cellulitis with bullae formation (19%). Concurrent spontaneous bacterial peritonitis was determined in 10 cases, seven with positive ascites cultures. Antibiotic therapy (either cephalothin with gentamicin or ceftriaxone alone) cured most of the bacteremic episodes. The overall case-fatality rate was 23.8%, but 75% of the deaths were observed in patients with skin manifestation. CONCLUSIONS: Patients with decompensated cirrhosis are susceptible to non-O1 V. cholerae bacteremia and should not ingest raw seafood or expose skin wounds to salt water. A high index of suspicion and early administration of antibiotics may lower the mortality rate.

Adult↗

PubMed1996

Risk factors associated with fulminant amebic colitis.

Amebic colitis is associated with serious complications and a high fatality rate if it progresses to its fulminant form. The purpose of this retrospective study was to determine the risk factors associated with fulminant amebic colitis. From February 1978 to February 1993, 60 adults were diagnosed with intestinal amebiasis at Chang Gung Memorial Hospital. Sixteen patients with massive bloody diarrhea, persistent systemic toxicity or signs of peritonitis were classified as having fulminant colitis, five of whom progressed to fulminant colitis after admission to the hospital. Forty-four patients with good responses to amebicides and without complications were classified as having moderate colitis. There was no amebiasis-related mortality among patients with moderate colitis. In contrast, five patients with fulminant colitis died. Early diagnosis and surgical treatment significantly decreased mortality when compared with conservative treatment. Significant factors associated with the development of fulminant intestinal amebiasis in univariate analyses were being male, age over 60 years, having an associated liver abscess, progressive abdominal pain, signs of peritonitis, leukocytosis, hyponatremia, hypokalemia and hypoalbuminemia. Only the factors of being over 60 years of age and hypokalemia were important in multivariate analyses. We conclude that early and extensive surgical treatment is mandatory for patients with typical presentations of fulminant amebic colitis on admission to the hospital, such as progression to peritonitis, persistent systemic toxemia and explosive bloody diarrhea. For other patients, especially the elderly and those with low serum potassium levels, close monitoring and observation for signs of fulminant colitis is important.

Adult↗

PubMed1996

Hypoxemia in a cirrhotic patient caused by hepatopulmonary syndrome: a case report.

Hepatopulmonary syndrome (HPS) is the triad of liver disease, pulmonary vascular dilatation, and abnormal arterial oxygenation. We report a case with progressive orthodeoxia and platypnea who was proven to have HPS after serial investigations, including autopsy. This 61-year-old male is a case of alcoholic liver cirrhosis without any documented cardiopulmonary disorders before. However, he suffered from progressive dyspnea in his last one-year life. During that period, progressive severe hypoxemia, orthodeoxia and platypnea were detected. Serial non-invasive diagnostic approaches, including two-dimensional contrast enhanced echocardiography and technetium-99m labeled macroaggregated albumin (MAA) lung perfusion scanning, were performed and showed positive evidence of intrapulmonary shunting. Direct evidence of intrapulmonary vascular dilatation was finally proven by autopsy. Although this syndrome is not rare, clinical awareness of the association between liver disease and arterial oxygen desaturation is still inadequate. We report a case proved by typical clinical manifestation and complete investigation and review the literature to emphasize this important disorder.

Cyanosis↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

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↗

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↗