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Biomedical subjects

S Pol

Publications and source records attributed to S Pol.

At least 109 records · Page 6Linked to original sources
PubMed1996

Alpha-interferon for chronic active hepatitis B in human immunodeficiency virus-infected patients.

OBJECTIVES: A pilot study was conducted to evaluate the efficiency of alpha-interferon treatment in chronic active hepatitis B in anti-HIV-positive patients. METHODS: Twenty-five patients with chronic active hepatitis (23 men and 2 women, mean age: 33 years) were included in the study. Viral infections were acquired by intravenous drug addiction in 2, homosexual relations in 22, and multiple heterosexual contacts in one. The mean CD4 cell count was 480 +/- 234/mL, 7 patients had p24 antigenemia, but none belonged to class C of the CDC classification. All patients were serum HBs Ag and HBV DNA-positive, and delta antigen and antibody negative. Patients received a 6-month course of alpha-interferon 2a, 6 MU subcutaneously three times per week. The mean follow-up after treatment was 15 months. Eighteen patients with serum anti-HIV antibodies, HBsAg and HBV DNA-positive, and chronic active hepatitis, who were not treated with interferon, were included as controls (mean follow-up: 29 months). RESULTS: Nine of the 25 patients (36%) lost serum HBV DNA (1, 2, 4, 6, and 8 months after the beginning of treatment in 1, 4, 1, 2 and 1 cases, respectively), and were considered responders. Only one of the responders developed serum anti-HBe during follow-up, despite the disappearance of HBe Ag in 2 and of HBs Ag in one. Loss of HBV DNA was not clearly associated with the immune status, since 3 of the 9 responders had p24 antigenemia and the 9 responders had a lower mean CD4 count (283 +/- 246/mm3) than non responders (454 +/- 437/mm3, NS). Three of the 18 patients (16.7%) in the control group had spontaneous loss of serum HBV DNA during follow-up. Thus, there was a 2.15-fold increase in HBV DNA loss in the anti-HIV-positive patients who received alpha-interferon, compared to those who did not. CONCLUSION: In HIV-positive patients treated with alpha-interferon, the rate of HBV DNA loss was not clearly different from that reported in immunocompetent patients. As severe HBV-related liver disease has previously been described in anti-HIV positive patients, at least in drug users, these results suggest that this treatment may be proposed whatever the immune status, at least in the absence of AIDS.

Adult↗
PubMed1995

[In situ hybridization for the detection of hepatitis C virus RNA in mononuclear cells of peripheral blood from infected patients].

In situ hybridization was used to investigate hepatitis C virus infection in peripheral blood mononuclear cells in 11 patients with chronic hepatitis. Using 35S labeled HCV-RNA probe, HCV-RNA positive and negative strands were observed in unstimulated cells of 3/11 patients; all 3 being treated with immunosuppressive drugs after orthotopic liver transplantation. HCV-RNA sequences were also identified in mononuclear cells obtained from 3 patients without immunosuppression, after stimulation of the cells with either phytohemagglutinin or pokeweed mitogen. In contrast, HCV-RNA was not found in 5 cases, where there was no liver transplantation or cell stimulation by mitogens. These results definitely assess infection of mononuclear cells by HCV. In addition, they demonstrate that mitogenic stimulation of infected cells increases HCV-RNA replication.

Adult↗
PubMed1995

Hepatitis C virus type 1b (II) infection in France and Italy. Collaborative Study Group.

OBJECTIVE: To analyze the distribution of hepatitis C virus (HCV) genotypes among patients positive for antibody to HCV (anti-HCV) according to age, severity of liver disease, and duration of infection; to investigate the influence of HCV genotypes on response to interferon-alpha therapy; and to study HCV viremia levels in relation to genotypes and severity of liver disease. DESIGN: Cross-sectional study. SETTING: 3 university hospitals and 2 research units. PATIENTS: 3 groups of French and Italian patients with chronic HCV infection and detectable serum HCV RNA: Group 1 included 35 patients with hepatocellular carcinoma; group 2, 71 patients with cirrhosis who did not have hepatocellular carcinoma; and group 3, 114 patients with chronic active hepatitis. 106 of the patients with chronic hepatitis or cirrhosis were treated with interferon-alpha (3 MU subcutaneously 3 times/wk for > or = 6 months). MEASUREMENTS: Genotyping by polymerase chain reaction with capsid-specific primers; serum HCV RNA by branched DNA (bDNA) signal amplification. RESULTS: Hepatitis C virus genotype 1b (II) was the most prevalent genotype (61.8%). In a univariate analysis, it was associated with older age (< 40 years, 47.4%; > or = 60 years, 80.4%; P = 0.001), longer duration of disease (< or = 10 years, 40.4%; > or = 20 years, 86.7%; P = 0.005), and cirrhosis with or without hepatocellular carcinoma (78.4% compared with 53.8% for chronic hepatitis; P < 0.001). Viremia levels did not differ between patients infected with HCV type 1b (II) and those infected with other HCV genotypes. Patients with HCV type 1b (II) responded to interferon-alpha therapy significantly less than did patients with other HCV genotypes (P = 0.01). In a multivariate analysis, age and cirrhosis were independently associated with HCV genotype 1b (II). Genotype and HCV viremia level were independent predictors of response to interferon-alpha therapy. CONCLUSIONS: The prevalence of HCV genotypes in French and Italian patients has been changing; the prevalence of HCV type 1b (II) infection has progressively decreased, although it still accounts for most HCV-related cirrhosis and hepatocellular carcinoma. High HCV viremia levels and HCV genotype type 1b (II) are independent predictors for poor response to interferon-alpha therapy and should be considered in the management of patients with HCV infection.

Adult↗
PubMed1995

The changing relative prevalence of hepatitis C virus genotypes: evidence in hemodialyzed patients and kidney recipients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection by the genotype 1b is significantly associated with a lower rate of response to interferon alfa and with severe liver disease (cirrhosis and hepatocellular carcinoma). This may reflect different intrinsic properties of this genotype 1b and/or chronological differences in the epidemiology of HCV genotypes. To address the issue of variations in genotypes prevalence, we studied in the present report the HCV genotypes of 60 hemodialyzed and kidney recipients according to the date of hemodialysis. METHODS: Anti-HCV antibodies were tested by a second-generation assay (enzyme-linked immunosorbent assay 2 and recombinant immunoblot assay 2). HCV RNA was detected by reverse-transcription polymerase chain reaction. Genotyping was performed by hybridization of type-specific probes to the amplified product from the 5' untranslated region. RESULTS: Genotype 1b accounted for more than two thirds of HCV infection in patients who underwent dialysis before 1977 but less than one third in those hemodialyzed after 1985. In contrast, other genotypes (3a, 4a, 5a) appeared in the 1980s. CONCLUSIONS: These data, obtained in an homogenous group of patients, show a changing pattern of HCV genotype prevalence over time and should be considered when discussing the potential clinical implications of HCV genetic variability.

Female↗
PubMed1995

Evidence of non-A, non-B, non-C infection in chronic hepatitis by polymerase chain reaction testing for hepatitis B and C viruses.

BACKGROUND/AIMS: Although hepatitis C virus is clearly the major cause of non-A, non-B acute and chronic hepatitis, there is a group of patients with histologically documented chronic hepatitis with no serological marker of hepatitis B and C, nor any other risk factors for liver disease. METHODS: We have investigated 17 well-characterized patients with chronic active hepatitis. HBV-DNA and HCV-RNA were tested by polymerase chain reaction in 17 serum samples and in six liver biopsies. RESULTS: Four of the 17 patients had serum HCV-RNA detectable by polymerase chain reaction, while none had HBV-DNA detectable by polymerase chain reaction. Three of the six liver samples gave a positive signal by cyclin A and HLA, and only these were considered for the study. One of the three was HCV-RNA positive, while none was HBV-DNA positive. CONCLUSIONS: Our results, obtained through careful elimination of all known risk factors for liver disease, strongly suggest that non-A, non-B, non-C hepatotropic virus(es) could be involved in some cases of chronic active liver disease.

Adolescent↗
PubMed1995

Immunotherapy of chronic hepatitis B by anti HBV vaccine.

Vaccine therapy is now used in various infectious diseases. The hepatitis B virus (HBV) leads to chronic infection in around 5% of patients with a high risk of chronic active hepatitis which may result in cirrhosis and hepatocellular carcinoma. The partial efficacy of antiviral therapies (40% of sustained inhibition of HBV replication), their cost, the numerous side effects and the immune-mediated pathology of HBV infection explain the emergence of new immune therapies in treating HBV infection. Experimental and clinical arguments are in favor of vaccine therapy in HBV chronic infection. Thirty-two consecutive chronic HBsAg carriers with chronic hepatitis and detectable serum HBV DNA were given 3 standard injections of the GenHevac B vaccine at one month intervals. Six months after the first injection, 12 patients (37.5%) had undetectable HBV DNA while 3 others showed significant decrease in HBV DNA titers. Eight of these 15 responders received a standard course of alpha-interferon (5 MU thrice weekly subcutaneously for 4 months) and all still had undetectable HBV replication. By contrast, among 13 (of the 17) non responders to vaccine who were given alpha-interferon, only 3 stopped HBV replication. In summary, serum HBV DNA disappeared in 18 of the 32 patients (53.1%) who were given vaccine therapy, with or without interferon. Vaccination was uneventful. Active immune therapy against HBV appears as efficient and less expensive than antiviral therapies in stopping HBV replication. Such a result should be confirmed by controlled randomized trials.

Animals↗
PubMed1995

Efficacy and tolerance of alpha-2b interferon therapy on HCV infection of hemodialyzed patients.

A high frequency (25%) of anti-hepatitis C virus (HCV) antibodies is observed in French hemodialyzed patients; this is associated with detectable viremia in 85% and results in chronic hepatitis in more than 90%. We conducted a pilot study to examine the tolerance and efficacy of alpha-2b Interferon therapy upon HCV infection in hemodialyzed patients. Nineteen anti-HCV positive hemodialyzed patients were given a standard alpha-2b interferon regimen (3 megaunits subcutaneously three times weekly, following each hemodialysis) over six months as a treatment of biopsy-proven chronic hepatitis (N = 16) or acute hepatitis (N = 3). Thirteen of these 19 had increased levels of aminotransferase at the time of treatment. Serum HCV RNA was tested qualitatively and quantitatively by the polymerase chain reaction and the bDNA test, respectively, at the beginning and at the end of antiviral treatment, and a third time at least six months after the end of therapy (mean follow-up 18 +/- 9 months). HCV genotype was determined in the 15 patients who had detectable HCV RNA before treatment. The biological response (long-term response, relapse or non-response) was defined as usual according to the serum aminotransferase levels during therapy and at least six months after. A post-treatment liver biopsy, allowing comparison with semiquantitative pathological scores, was performed in 14 patients. Only one of the 19 treated patients did not complete therapy because of poor tolerance, while 18 of the 19 fairly tolerated a complete six month course of alpha-2b interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Serum hepatitis C virus (HCV) RNA: a reliable tool for evaluating HCV-related liver disease in anti-HCV-positive blood donors with persistently normal alanine aminotransferase values.

BACKGROUND: The significance of hepatitis C virus (HCV) antibodies in blood donors with persistently normal alanine aminotransferase (ALT) levels requires evaluation. STUDY DESIGN AND METHODS: The serum and the liver were assayed for HCV RNA. Liver histology was analyzed in 14 HCV-positive subjects who had repeatedly normal ALT values over a follow-up period of at least 3 months. RESULTS: HCV RNA was not detected in liver and serum, and liver histology showed minimal changes in more than one-half of the subjects (8/14), even if third-generation recombinant immunoblot assay was positive; this demonstrated that HCV can be eradicated spontaneously. Moderately histopathological liver lesions were usually found in HCV RNA-positive subjects (6/14), but one subject had active disease that required interferon therapy; this shows that chronic hepatitis may be present in HCV-positive individuals despite repeatedly normal transaminase values. HCV genotypes other than 1b (II) were usually identified, and the presence or absence of serum and liver HCV RNA correlated completely in all 14 patients. CONCLUSION: Serum HCV RNA should be assayed in those HCV-positive donors having repeatedly normal transaminase activity; if it is positive, indicating an ongoing HCV infection, a liver biopsy should be performed to measure the degree of the liver disease and determine the appropriate antiviral therapy.

Adult↗
PubMed1995

Value of liver biopsy for the rapid diagnosis of infection in human immunodeficiency virus-infected patients who have unexplained fever and elevated serum levels of alkaline phosphatase or gamma-glutamyl transferase.

We prospectively determined the value of liver biopsy for microbiological diagnosis of infection in patients infected with the human immunodeficiency virus (HIV) who had unexplained fever and whose serum levels of alkaline phosphatase or gamma-glutamyl transferase were at least 1.5 times the upper limit of normal. From December 1989 to December 1991, 108 HIV-infected patients were referred to the Liver Unit at Hôpital Laënnec (Paris) with liver abnormalities related to viral hepatitis (generally chronic), AIDS-related sclerosing cholangitis, or nonspecific lesions (detected on histologic examination). Twenty-four patients had unexplained fever and increased levels of alkaline phosphatase or gamma-glutamyl transferase, and none had evidence of hepatobiliary disease. All 24 patients had undergone routine microbiological tests to determine the cause of their chronic fever. The results of all microbiological tests were negative. We performed liver biopsies for these 24 patients and examined the specimens by means of standard direct microbiological techniques; in addition, the specimens were cultured, the specimens were analyzed by standard histopathologic methods, and specific histologic studies for fungi, mycobacteria, and viruses were performed. A microbiological diagnosis was made in 13 (54%) of the 24 cases within 12 hours to 3 days of the liver biopsy. In conclusion, liver biopsy is a powerful diagnostic tool for rapid diagnosis of infection in HIV-infected patients who have unexplained fever and abnormal liver function test results.

AIDS-Related Opportunistic Infections↗
PubMed1995

Clinical impact of drug addiction in alcoholics.

Careful interviewing of alcoholics who wish to undergo alcohol withdrawal programmes reveals that some are past intravenous drug abusers. As these two potentially hepatotoxic types of substance abuse could cause liver disease or influence its clinical course, we studied biological, histological and virological features in 26 alcoholics with a past history of intravenous (i.v.) drug abuse, compared with paired controls (alcoholics without i.v. drug abuse). There were no differences with regard to routine liver test results. In contrast, the former drug abusers had a significantly higher prevalence of serum markers of hepatitis C (76.9%) and hepatitis B viruses (76.9%) than the other patients (16.7 and 12.5%, respectively). Eight patients, all of whom were HBs Ag negative, were positive for serum HBV-DNA; three were former drug abusers and five were not, giving an overall prevalence of HBV markers in the two groups of 80.8 and 25%, respectively. Two former drug abusers had anti-HIV antibodies and one had anti-hepatitis delta virus antibodies. Ten of the 17 former drug abusers who underwent liver biopsy had histological signs of viral infection. These data underline the need for careful interviews of alcoholic patients, together with serological tests for viral infections and histological analysis of the liver, as some will have liver-damaging viral diseases and may be candidates for anti-viral (i.e. interferon) treatment.

Adult↗
PubMed1995

In vivo and in vitro expression of defective hepatitis B virus particles generated by spliced hepatitis B virus RNA.

The mechanisms involved in hepatitis B virus (HBV) persistence are still poorly understood. We have previously shown that the encapsidation of the singly spliced 2.2 kb-HBV RNA leads to the secretion of circulating HBV defective particles in patients with chronic hepatitis. We have now investigated the presence of the HBV defective particles in sera from patients with acute and chronic hepatitis, using polymerase chain reaction. These defective particles were detected in a larger amount in sera of patients with acute hepatitis that progressed to chronic hepatitis, or had already developed chronic hepatitis, as compared with those who recovered from acute hepatitis (the increase was estimated to be an average of 50-fold). In addition, we showed that the presence of these defective HBV particles is closely associated with the chronic course of hepatitis B virus infection and with viral multiplication. We also analyzed viral RNAs and proteins synthetized after in vitro transfection of Huh7 cell line with the corresponding defective hepatitis B virus DNA molecule. We showed that expression of the defective hepatitis B virus DNA alone leads to a marked intracellular accumulation of the major core protein (HBcAg) and to an increased secretion of hepatitis B e antigen (HBeAg). These observations may be consistent with a role of these defective hepatitis B virus (HBV) particles in viral persistence.

Base Sequence↗