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Biomedical subjects

M Reynes

Publications and source records attributed to M Reynes.

At least 55 records · Page 3Linked to original sources
PubMed1994

The course of hepatitis C virus infection after liver transplantation.

Hepatitis C virus-induced liver disease is becoming a main indication for liver transplantation. Recurrence of hepatitis after transplantation has been reported, but its long-term consequences are unknown. Seventy-nine patients positive for hepatitis C virus (group 1) and 106 subjects negative for hepatitis C virus antibody (group 2) with a mean follow-up of 4 yr were retrospectively studied by means of serology, nested polymerase chain reaction and branched-DNA technology before and after liver transplantation. The actuarial rates of hepatitis C virus-related acute hepatitis were 72% and 20% at 4 yr in groups 1 and 2, respectively. Progression to chronic active hepatitis occurred in 61% and 36% of the subjects within 3 yr of the onset of recurrent and acquired hepatitis, respectively. No case of acute graft failure and two cases of cirrhosis were related to recurrent or acquired hepatitis C virus liver disease. Hepatitis C virus RNA levels were significantly increased in cases of hepatitis after transplantation. In contrast, the pretransplant hepatitis C virus RNA level was not predictive of recurrence. Our results establish the general persistence of hepatitis C virus infection after liver transplantation, the frequency and the severe course of recurrent liver disease. However, liver transplantation in hepatitis C virus antibody-positive patients still has a good medium-term prognosis.

Adult↗
PubMed1994

Pretransplantation interferon treatment and recurrence of hepatitis B virus infection after liver transplantation for hepatitis B-related end-stage liver disease.

Orthotopic liver transplantation in patients with hepatitis B-related cirrhosis is commonly complicated by reinfection with the hepatitis B virus, with rapidly progressive liver disease and poor survival rate. We assessed the efficacy of prior therapy with recombinant interferon-alpha on the prevention of posttransplantation hepatitis B virus reinfection. Twenty-two patients with hepatitis B-related cirrhosis waiting for liver transplantation received 3 MU (decreased to 1.5 MU in cases of intolerance) of recombinant interferon-alpha until transplantation. The rates of posttransplantation hepatitis B virus reinfection and survival in this group were compared with those in a group of 26 patients previously given transplants for the same disease but not given interferon therapy. The same protocol of HBs antibody passive immunoprophylaxis was applied after transplantation in both groups. Recombinant interferon-alpha was administered for 14 +/- 7 wk. The treatment had an antiviral effect, with disappearance of serum hepatitis B virus DNA in seven of the eight patients initially positive for hepatitis B virus DNA and disappearance of HBeAg in two of the three patients initially positive for HBeAg. Serum hepatitis B virus DNA remained detectable with polymerase chain reaction at transplantation in 56% of the interferon-treated patients. After transplantation, hepatitis B virus reinfection was more frequent in polymerase chain reaction-positive than in polymerase chain reaction-negative patients (78% vs. 17%, p < 0.05). One patient's condition deteriorated during interferon treatment; this patient was not given a transplant. Two patients (in whom hepatitis B virus DNA disappeared from serum) improved so markedly during treatment that they were not given transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Hepatitis C virus RNA and hepatitis B virus DNA in serum and liver of patients with fulminant hepatitis.

BACKGROUND: The role of hepatitis C virus (HCV) in the development of fulminant hepatitis is poorly understood. METHODS: The polymerase chain reaction was used to detect HCV RNA and hepatitis B virus (HBV) DNA in serum and liver of 40 patients with fulminant or subfulminant hepatitis. RESULTS: HCV RNA was detected in none of the 23 subjects with hepatitis B surface antigen (HBsAg)-negative hepatitis of unknown etiology. HBV DNA was found in 1 of these 23 subjects. In contrast, 8 of the 17 patients with HBsAg-positive hepatitis were HCV RNA positive. Among the latter, 5 had immunoglobulin (Ig) M antibody to hepatitis B core antigen (anti-HBc) and thus were acutely coinfected by HBV and HCV, whereas 3 others without IgM anti-HBc had superinfection by HCV. The active replication of HCV in the liver was shown by detection of high titers of HCV RNA and of negative-stranded HCV RNA. CONCLUSION: This investigation therefore shows no evidence of a role for HCV infection in sporadic cases of fulminant hepatitis without defined etiology. However, it suggests that HCV might be implicated in a significant number of patients with HBV-related fulminant hepatitis.

Adolescent↗
PubMed1992

Prolongation of heart allograft survival in rats by interferon-specific antibodies and low dose cyclosporin A.

Interferons (IFNs) are important cytokines which exhibit antiviral, antitumor, anticellular, as well as immunoregulatory activities. Among these multiple activities, IFNs are potent inducers of MHC antigen expression of a great variety of cells, helper and maturation factors in B-cell antibody production, and macrophage function. IFNs may therefore play a critical role in triggering antigen recognition and allograft rejection. Cyclosporin A (CyA) is a potent immunosuppressor which selectively inhibits helper T-lymphocyte proliferation in response to alloantigen presentation. CyA has been reported to inhibit interleukin 2 and IFNgamma production by helper T lymphocytes. In addition, CyA may induce monocyte production of prostaglandin E2, which then reduces MHC class II expression on endothelial cells, monocytes, and macrophages. However, the clinical use of CyA is plagued by its toxic (in particular nephrotoxic) side-effects. These toxic effects are clearly dose-related. It may be very important to develop new products which can act synergistically with CyA to inhibit lymphokine production. The aim of this study was to investigate the effects of combined IFN-specific antibodies and low dose CyA on cardiac allografts in inbred strains of rats.

Animals↗
PubMed1992

Non specific increased expression of class I major histocompatibility complex (MHC) antigens on rat liver grafts.

Major histocompatibility complex (MHC) antigens play a major role in the rejection reaction and their increased expression may increase the host response to the foreign graft. Several clinical and experimental studies have demonstrated increased expression of MHC antigens on the different cell components of liver allografts during rejection. However modified expression of MHC antigens may also occur in certain liver diseases, after cholestasis or on a regenerating liver. In this experimental study in inbred rats, we compared the expression of MHC antigens on liver cells during rejection and non-immunological situations (cholestasis, cytolysis, regeneration).

Animals↗
PubMed1992

Monokine gene expression in normal human liver: selective involvement of the portal compartment.

Monokines play a major role in the regulation of hepatocyte functions. To document a possible in situ production of these mediators under physiological conditions, expression of IL-1 beta and of IL-6 genes was analyzed by in situ hybridization in four histologically normal human livers. We detected cells containing IL-1 beta mRNA or IL-6 mRNA in all cases. Cells expressing either the IL-1 beta gene or the IL-6 gene were found with equal frequency and were similarly distributed. Although present in all liver compartments, they were selectively enriched in portal areas, in which they were detected both in endothelial positions and in perivascular connective tissues. Few positive cells were observed in hepatic lobules, most of them being located in the walls of centrolobular veins, in an endothelial position. Subcapsular cells were also shown to express monokine genes. The location of positive cells and their pattern of labelling suggested that macrophages, fibroblasts and endothelial cells were the main cell populations expressing monokine genes. In contrast, Kupffer cells, biliary epithelial cells and hepatocytes did not express monokine genes. No marker of immune activation other than monokine gene expression was detected in these histologically normal livers. The expression of the IL-1 beta gene and of the IL-6 gene may be induced by gut-derived LPS, and could play a role in the modulation of hepatocyte function in normal liver.

Gene Expression↗
PubMed1992

Reinfection of liver graft by hepatitis C virus after liver transplantation.

We have investigated hepatitis C virus (HCV) viremia before and after orthotopic liver transplantation (OLT). 38 patients were examined; 16 were anti-HCV positive and 22 anti-HCV negative pre-OLT in a RIBA-2 test (Ortho Diagnostic Systems Inc., Westwood, MA). HCV-RNA was detected using a modified nested polymerase chain reaction in 14/38 and 10/38 patients before and after OLT, respectively. 7 of these 14 subjects who were HCV-RNA positive before OLT were also positive for serum hepatitis B surface antigen. After OLT, six patients became HCV-RNA positive, likely as a result of transfusions, while four developed a probable recurrence of HCV infection. Infection of the liver graft by the same strain of HCV was indeed demonstrated by sequence analysis of a hypervariable domain (in the envelope region) in two cases. This establishes the possibility of HCV recurrence and shows the usefulness of polymerase chain reaction as the only assay currently capable of identifying HCV infection after OLT.

Base Sequence↗
PubMed1992

Effect of storage temperature on early graft function following liver transplantation.

The effect of storage temperature on early graft function following liver transplantation was investigated by analyzing the results following transplantation during three periods in which different techniques for graft storage were used. The techniques involved ice-packing (period 1), storage in a standard operating room refrigerator without ice-packing (period 2) and storage in an accurately controlled refrigerator without ice-packing (period 3). In period 2 there was a significantly higher incidence of histological lesions, primary non-function and retransplantation compared to periods 1 and 3. It was concluded that this was due to inaccurate control of the standard refrigerator in period 2, thus allowing the temperature of the graft to increase, while in periods 1 and 3 the graft temperature was kept close to 4 degrees C by ice-packing and accurate refrigerator control, respectively. These results demonstrate that accurate control of storage temperature is important in terms of subsequent graft function. This may become more important as storage times are progressively increased with the use of UW solution.

Cold Temperature↗
PubMed1991

Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients.

110 HBsAg-positive patients underwent orthotopic liver transplantation and received long-term anti-hepatitis B virus (HBV) passive immunoprophylaxis with anti-HBs immunoglobulin. During a mean follow-up period of 20 months, all patients became HBsAg negative after transplantation but circulating HBsAg reappeared in 25 (22.7%). Overall 1-year survival was 83.6% and overall 2 year actuarial recurrence of HBsAg was 29% (59% after posthepatitis B cirrhosis, 13% after posthepatitis B-delta cirrhosis, and 0% after fulminant hepatitis B). Patients with HBV cirrhosis who were HBV-DNA positive had a much greater risk of HBsAg recurrence than patients who were HBV-DNA negative (96% vs 29% at 2 years). Reappearance of HBsAg was associated with evidence of HBV replication and abnormal histological findings in the graft. Long-term passive anti-HBV immunoprophylaxis significantly reduced HBV reinfection and improved survival in patients without evidence of active HBV replication before orthotopic liver transplantation.

Adolescent↗
PubMed1991

Genes for interleukin-1, interleukin-6, and tumor necrosis factor are expressed at markedly reduced levels in the livers of patients with severe liver disease.

The genes for interferon (IFN) alpha, IFN gamma, IL-1 beta, IL-6, and TNF alpha were transcribed at readily detectable levels both in liver biopsies from individuals with normal liver function and in samples of normal viable liver taken for transplantation. These results provided evidence for the concept that such multifunctional cytokines play a role in homeostasis in normal human tissues. In normal human liver, in situ hybridization studies showed that, in the absence of a detectable inflammatory response, both hepatocytes and mononuclear cells exhibited a similar degree of expression of IL-6 mRNA in keeping with the finding that IL-6 is produced by cells of different lineages. The levels of IL-1, IL-6, and TNF mRNA were found to be markedly reduced in extracts of the livers of patients with primary biliary cirrhosis and other forms of autoimmune liver disease at a time when extensive liver lesions were apparent, compared to the levels of expression of these cytokines in the livers of normal individuals. The reduced expression of IL-1, IL-6, and TNF mRNAs appeared to be a specific effect and not due to a general reduction in RNA synthesis as the IFN alpha, IFN gamma and actin mRNAs were expressed at similar levels in both normal and diseased livers. The levels of IL-1 beta, IL-6, and TNF mRNAs were also reduced in samples of liver from a patient with a drug induced fulminant hepatitis suggesting that this specific pattern of altered cytokine gene expression was characteristic of the advanced stage of severe liver disease.

Autoimmune Diseases↗