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S Pol

Publications and source records attributed to S Pol.

At least 91 records · Page 5Linked to original sources
PubMed1997

Hepatitis C virus-related fibrosing cholestatic hepatitis after renal transplantation.

Fibrosing cholestatic hepatitis is a well-described syndrome in patients with immunodeficiency and chronic hepatitis B. It is clinically, biologically, and histologically characterized by rapidly progressive hepatic failure, a mildly elevated serum aminotransferase level, an extensive periportal fibrosis associated with intense cholestasis, mild inflammatory cellular infiltrate, no cirrhosis, and a high hepatocellular level expression of B viral antigens. This syndrome reflected a direct hepatocytopathic injury linked to high intrahepatic viral antigen expression. Because the syndrome of fibrosing cholestatic hepatitis has not been described in chronic hepatitis C, we report the first well-characterized case in a renal transplant patient with chronic hepatitis C and discuss the clinical and pathogenic implications of such a syndrome in this setting.

Adult↗
PubMed1997

Hepatitis C virus genotypes in French haemophiliacs: kinetics and reappraisal of mixed infections.

The distribution and kinetics of hepatitis C virus (HCV) genotypes and the prevalence of mixed infections were studied in a group of 45 French patients with haemophilia A or B or von Willebrand's disease, 21 of them being anti-human immunodeficiency virus (HIV) positive; genotyping was carried out by three methods based on the core, 5' untranslated region (5'UTR), and the detection of type-specific NS4 antibodies. Genotyping of the 5'UTR revealed genotypes 1a (n = 10), 1b (n = 13), 2a (n = 3), 2b (n = 4), 2NC (n = 3), 3a (n = 10), and two mixed infections (1a + 1b and 3a + 2). Five of 33 patients showed a change from one HCV genotype to another. The core genotyping assay showed 8 of 45 mixed infections: 6/8 1a + 1b and 2/8 3a + 2. Sequencing of core polymerase chain reaction (PCR) products showed that mixed infection 1a + 1b could be explained by nonspecific annealing of the 1b primer to type 1a sequence. By designing new primers whose sequence was more specific to HCV types 1a and 1b, we could confirm 1a + 1b mixed infection in only one of six cases. Serotyping assay showed for 17 of 21 anti-HIV negative patients a concordance with the 5'UTR genotype; however, only 6 of 19 anti-HIV positive patients showed detectable serological reactivity. In summary, we have observed a similar HCV genotype distribution between our haemophilic group and the French anti-HCV positive patients. The study demonstrates the difficulties of assessing with the presently available genotyping and serotyping assays the real prevalence of mixed infections in multiply transfused patients.

Antigens, Viral↗
PubMed1997

Hepatitis C virus genome complexity correlates with response to interferon therapy: a study in French patients with chronic hepatitis C.

Recent studies performed in Japan have suggested that hepatitis C virus (HCV) genome heterogeneity might be taken as a predictive virological parameter of response to interferon alfa (IFN-alpha) treatment. However, there is presently no information on the impact of this virological parameter in patients from Western countries infected by different HCV genotypes. We have investigated this issue by using amplification of HCV E2 hypervariable region 1, followed by single-strand conformation polymorphism assay (PCR-SSCP). We have studied 95 French patients infected with various genotypes and treated with IFN-alpha-2b. We analyzed the impact of the following parameters by univariate and multivariate analyses: HCV heterogeneity, HCV genotype, viral load, and liver histology in response to therapy. Age >40 years (P < .01), viral load >35 x 10(5) Eq/mL (P < .01), genotype 1 (P < .01), and a number of SSCP bands >3 (P < .001) were significantly associated with nonresponse or relapse; cirrhosis was associated with nonresponse. In multivariate analysis, three variables were independently associated with the absence of long-term response: SSCP bands >3, genotype 1, and viral load >35 x 10(5) with odds ratios of 19, 7.5, and 11.8, respectively. Our data establish the major importance of HCV genome heterogeneity in patients infected with both HCV types associated with low (genotype 1b) or high (genotype 3a) response to IFN-alpha.

Adult↗
PubMed1997

Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer.

The prognosis for patients with primary liver cancer (PLC) often depends on tumor recurrence and the development of extrahepatic metastases, particularly after liver transplantation. We have developed a sensitive test to detect both spontaneous circulation of tumor cells and the spread of liver cells due to chemoembolization and alcoholization. Reverse-transcription polymerase chain reaction was used to search for cells expressing alpha-fetoprotein (AFP) messenger RNA in the peripheral blood of 84 patients with PLC and 102 controls (55 patients with chronic hepatitis and/or cirrhosis, 10 patients with benign liver tumors or liver metastases from intestinal cancers, and 37 healthy individuals). By spiking the blood of healthy volunteers with HepG2 cells, we assessed the sensitivity limit: one HepG2 cell mixed with 10(7) leukocytes. All 102 controls tested negative. In contrast, 28 patients (33.3%) with PLC tested positive. Positivity for the test was significantly associated with portal thrombosis, tumor size, intravascular tumor emboli, serum AFP level, and extrahepatic metastases. Patients were followed up for a mean period of 39 +/- 51 weeks: the probability of developing extrahepatic metastases was significantly higher in positive than in negative patients. Eighteen negative patients with PLC were tested before, 1 hour after, and 24 hours after locoregional therapy: 9 tested positive either 1 or 24 hours after alcoholization or chemoembolization. In conclusion, we have developed a highly specific and sensitive test to detect circulating tumor cells in patients with PLC. This test is likely to be clinically useful in evaluating the risk of developing extrahepatic metastases and the possibility of iatrogenic spreading of liver-derived, possibly tumorous, cells.

Female↗
PubMed1997

Mutations in the nonstructural 5A region of hepatitis C virus and response of chronic hepatitis C to interferon alfa.

BACKGROUND & AIMS: Mutations in hepatitis C virus (HCV) nonstructural protein 5A (NS5A) may correlate with response to interferon in Japanese patients with chronic hepatitis C. The aim of this study was to examine whether these findings could be expanded to European patients infected with genotypes associated to low (1b) or high (3a) response rates. METHODS: Pretreatment serum samples of 66 patients with chronic HCV infection, 48 infected with genotype 1b and 18 with 3a, were analyzed. RESULTS: Among patients infected with genotype 3a, 1 of 7 long-term responders and none of 11 nonresponders showed NS5A amino acid mutations. Among patients infected with genotype 1b, all 7 long-term responders, but also 27 of 41 nonresponders, showed NS5A mutations. There was no correlation between number of mutations and response to therapy. In 10 patients, sequences obtained before and after treatment were compared and failed to show any change. Serum HCV RNA levels did not differ between patients with and without mutations in NS5A sequence. CONCLUSIONS: No significant correlation was found in patients infected with genotypes 1b or 3a between NS5A sequence and response to interferon alfa. NS5A mutations do not correlate with viral load. Changes in this region were not found during interferon alfa treatment.

Adult↗
PubMed1997

[Clinical significance of detection and quantification of hepatitis C virus RNA in hemodialysis: proposal for a rational diagnostic strategy].

Viral infections due to hepatitis C virus in hemodialysis patients are frequent and have a potential risk of progression towards chronicity. Biochemical and viral markers of infection, are transaminases level, anti-HCV serology and the detection of HCV RNA, respectively. A rational strategy based on routine use of these three diagnostic tools is proposed in order to avoid unnecessary assays and to increase in the case of health cost control, the cost/efficacy ratio. The latter is set up, in the sero-negative hemodialysed, on the early detection of infection by the hepatitis C virus in order to consider of a therapeutic which is able to cure patients and to avoid the ineluctable passage towards chronicity; in hemodialysed with positive HCV serology, the detection of HCV RNA allows to establish the infectiosity status of these hemodialysis patients. It is therefore very important to evaluate prospectively this diagnosis approach in hemodialysis patients.

Genotype↗
PubMed1996

The long-term virologic and pathologic impact of renal transplantation on chronic hepatitis B virus infection.

In an attempt to evaluate the long-term reciprocal impact of renal transplantation on hepatitis B virus infection, we analyzed the clinical, virologic, and pathologic features of 151 HBsAg-positive kidney transplant recipients. The spontaneous disappearance rates of HBsAg, HBeAg, and HBV DNA during a median follow-up of 125 months (range 1 to 320) were 3, 30.6, and 3%, respectively, figures lower than in the general population. A high rate of persistent viral replication (50%) and reactivation (30%) was noted. Noteworthy was the high frequency of histologic deterioration (85.3%), accompanied by cirrhosis in 28% and by hepatocellular carcinoma in 23% of the patients with cirrhosis. Co-infection by hepatitis C and B viruses was significantly associated with histologic worsening. Liver disease was the leading cause of death (36.6%), especially in patients with cirrhosis. Despite persistent viral replication, histopathologic deterioration, and liver-related overmortality, there were paradoxically no significant differences in the survival of these 151 HBsAg-positive compared with 1247 HBsAg-negative kidney recipients--however, allograft actuarial survival was better in the former than in the latter group (P=0.0006). Chronic hepatitis B infection is not a contraindication to renal transplantation in the absence of cirrhosis. The presence of cirrhosis should lead either to dialysis continuation or to a combined liver/kidney transplantation, in the absence of viral replication.

Adult↗
PubMed1996

Azathioprine hepatitis in kidney transplant recipients. A predisposing role of chronic viral hepatitis.

Influence of viral liver diseases on the occurrence of azathioprine hepatitis was evaluated in 21 kidney transplant recipients. Diagnosis of azathioprine hepatitis was always based on jaundice, which disappeared after azathioprine withdrawal in 18 patients and after azathioprine dose reduction in 3 patients. Histopathological diagnosis of azathioprine toxicity was ascertained in 14 patients. Rechallenge with azathioprine performed in 4 patients, within 2-4 months after the first jaundice episode, resulted in relapse of jaundice in all cases. Viral hepatitis B virus and hepatitis C markers were present in all 20 tested patients (serum hepatitis B surface antigen in 6 patients and anti-HCV antibodies in 17 patients). Biopsy-proven chronic hepatitis was observed in 18 patients, including 14 chronic active hepatitis, 3 chronic persistent hepatitis and cirrhosis in 1. In kidney transplant recipients, azathioprine hepatitis seems to be facilitated or induced by hepatitis B virus or hepatitis C virus chronic hepatitis. Azathioprine reduction or withdrawal should therefore be combined with the diagnostic evaluation and the treatment of viral liver diseases.

Adult↗
PubMed1996

Reciprocal interactions between human immunodeficiency virus and hepatitis C virus infections.

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same routes of transmission, which explains the high rate of HCV and HIV coinfection (approximately 9%). HIV/HCV coinfection leads to high rates of indeterminate recombinant immunoblot assay patterns and seroreversion; high levels of viral replication; and a more severe histopathologic course. By contrast, HCV infection does not seem to accelerate the progression of HIV infection. Interferon alpha (IFN-alpha) in coinfected patients leads to a similar rate of primary responses, but sustained responses are less frequent. The potential severity of hepatitis C virus infection evidences the need for early diagnosis. Liver biopsy should be performed for all HCV RNA-positive patients in order to evaluate the activity of the liver disease. Given the poor efficiency of IFN-alpha in terms of sustained response in HIV-infected patients, reinforced therapeutic procedures (long-term administration of IFN-alpha or combined ribavirin/IFN-alpha) should be proposed, at least for those patients with severe liver disease.

AIDS-Related Opportunistic Infections↗
PubMed1996

Effectiveness and tolerance of interferon-alpha 2b in the treatment of chronic hepatitis C in haemodialysis patients.

Twenty-five per cent of haemodialysed patients carry anti-HCV antibodies; these antibodies are associated with detectable viraemia in 85% and chronic hepatitis in 90% of subjects, despite normal transaminases in more than half of them. This underlines the importance of antiviral therapy. We evaluated the tolerance and effectiveness of a classic interferon (IFN) treatment (3 MU three times a week for 6 months, subcutaneously) in 19 haemodialysis patients presenting with anti-HCV antibodies and chronic (n = 16) or acute (n = 3) hepatitis. Thirteen of those 19 patients had elevated transaminases. Viraemia C was detected by genome amplification (PCR) and by the bDNA test before and after interferon therapy as well as 6 months at least after the end of INF treatment. Response (defined as liver enzyme normalization) was noted in 11 (84.6%) of the 13 patients with elevated transaminases; at the end of follow-up, six exhibited long-term response and five had relapsed, HCV-RNA was detected in 15 of the 19 patients before IFN therapy and remained positive in 7/15 initially viraemic patients at the end of treatment. Hepatitis C RNA was detected at the last follow-up visit (mean follow-up duration 18 +/- 9 months) in 12 of the 15 initially viraemic patients. Liver histology was improved in most patients, regardless of their biological response. One patient could not complete the 6-month course because of clinical and haematological adverse events. In the six patients with strictly normal transaminases, HCV RNA was detectable in 4/6 patients before treatment, in 2/4 viraemic patients at the end of treatment, and in 4/4 at the last follow-up visit. All pathological signs disappeared in four of the five patients who had no detectable HCV-RNA before IFN therapy. To conclude: (i) interferon-alpha exhibits satisfactory effectiveness and tolerance in haemodialysed patient; (ii) HCV replication recurs in most of these patients despite histological improvement; (iii) interferon-alpha can be effective even in patients with chronic hepatitis and no detectable HCV-RNA.

Antibodies, Viral↗
PubMed1996

[Primary non-Hodgkin's lymphomas of the liver in human immunodeficiency virus infected patients. Three cases].

The occurrence of primary non Hodgkin's lymphoma of the liver has rarely been reported in patients with the human immunodeficiency virus infection. We report 3 cases in these patients, presenting with a single liver tumor in 2 cases and multiple tumors in one case. Diagnosis was made by guided-biopsy. Histologically, there was B diffuse large cell lymphoma in 2 cases, and immunoblastic lymphoma in one case. In one case, RNA of Epstein-Barr virus was found in the nucleus of tumor cells by in situ hybridization. No extrahepatic localization was found in any of the 3 cases. One patient died one week after diagnosis, but the 2 other patients were treated by chemotherapy and were still alive 6 and 30 months later. In patients infected by human immunodeficiency virus, primary non Hodgkin's lymphoma should be investigated in case of liver tumor in order to provide early treatment.

AIDS-Related Opportunistic Infections↗