[Hepatotropic virus and renal transplantation].
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Graft Survival↗
Biomedical subjects
F Carnot
Publications and source records attributed to F Carnot.
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↗
High levels of DNA adducts in human colon are associated with colorectal cancer.
Colon cancer is one of the most frequent causes of cancer death in western countries. Epidemiological studies suggest that colorectal cancer can be attributed, at least in part, to carcinogens and mutagens present in the diet and/or the environment. The covalent binding of these xenobiotics or their reactive metabolites to DNA is believed to initiate this chemical carcinogenesis. In the present study, using a 32P-postlabeling method, we investigated DNA adduct levels in control colons from patients without colorectal adenocarcinoma and in nontumoral and tumoral tissues from patients with colorectal adenocarcinoma. Our results show that the DNA adduct level is significantly higher (P < 0.001) in nontumoral than in control or tumoral colon samples. For the first time, we demonstrate in humans that the presence of numerous adducts in colonic mucosa is associated with colorectal cancer, a finding in agreement with the importance of chemical factors in causing this disease; therefore, after confirmation of the link between DNA adducts and colorectal cancer, the measurement of DNA adduct levels in colon samples could constitute a useful approach to the early detection of colorectal cancer.
Adenocarcinoma↗
Intrinsic infiltrating intramuscular laryngeal lipoma.
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Humans↗
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↗
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↗
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↗
Immunohistochemical detection of bcl-2 protein in thymoma.
The protooncogene bcl-2 encodes a protein that inhibits apoptosis. The protein is expressed in most epithelial cells of the fetal thymic medulla but, to the best of our knowledge, no data are available on bcl-2 expression in thymoma. Expression of bcl-2 protein was analysed in 30 cases of thymoma by immunohistological staining of paraffin-embedded tissue. All cases were examined and classified according to the Salyer and Eggleston and the Müller-Hermelink classification. In four cases, the protooncogene bcl-2 was abnormally expressed in spindle cells of pure medullary thymoma, whereas the non-spindle cells in mixed and in cortical thymoma were negative. All the lymphocytes were also strongly positive in medullary thymoma while a few lymphocytes showed light staining in other thymomas.
Adult↗
Site-directed bronchoalveolar lavage and transbronchial biopsy in HIV-infected patients with pneumonia.
We have assessed the diagnostic value of site-directed bronchoalveolar lavage (BAL) and combined transbronchial biopsy (TBB) in 29 HIV-infected patients with localized pneumonia, in whom a previous BAL was nondiagnostic and in whom improvement did not occur with empiric antibiotic therapy. All patients but three had a CD4 cell count < 100/microliters. A definite diagnosis could be reached in 26 of 29 (90%) individuals, including 24 pathogens. Neither the radiologic pattern nor the type of Pneumocystis carinii (PC) prophylaxis could predict the positivity of either one of these two diagnostic procedures. Site-directed BAL alone allowed a diagnosis in infection in eight (28%) cases. TBB alone led to diagnosis in eight (28%) cases, including three PC and two toxoplasma gondii, undiagnosed by the site-directed BAL. Both techniques were positive and in agreement in 10 (34%) cases. The majority of the diagnosis led to a specific treatment. Therefore, the patients' survival was positively altered by the procedure. In conclusion, the performance of site-directed BAL and combined TBB markedly optimizes the diagnostic yield of each of these procedures performed separately in HIV-infected patients with localized pneumonia.
Adult↗
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↗
Impact and evolution of peliosis hepatis in renal transplant recipients.
Peliosis hepatis and hepatic sinusoidal dilatations are rare vascular liver diseases that occur at increased frequency in kidney transplant recipients. We retrospectively evaluated in kidney transplant recipients the natural history of vascular liver diseases, their impact on patient and graft survival, and the influence of AZA withdrawal. Between 1970 and 1990, vascular liver disease was diagnosed in 32 cadaver kidney transplant recipients 1-128 months after transplantation (mean 41 months). Diagnosis was based on histology in all cases. Patients received conventional immunosuppression (high dose steroids and AZA). Twenty patients had a minor form (sinusoidal dilatations or focal peliosis), while 12 had a major form (diffuse peliosis) of vascular hepatic disease. Two patients were lost to follow-up and 1 died at the time of diagnosis. In 12 patients (group 1), AZA dosage remained unchanged, while it was interrupted at the time of diagnosis in 17 patients (group 2). Five group 1 patients underwent serial liver biopsies, which showed persistence of vascular hepatic disease in 3 (with regenerative nodular hyperplasia in 1) and disappearance in 2 patients. Eight group 2 patients underwent serial liver biopsies, which showed disappearance of vascular hepatic disease in 6 patients and persistence in 2. Moreover, regenerative nodular hyperplasia was noted in 1 case, perisinusoidal fibrosis in 1 case, and cirrhosis in 6 cases. Three patients of group 1 and 11 patients of group 2 returned to dialysis a mean of 21 and 39 months after diagnosis, respectively. Eight patients died and death was clearly associated with major peliosis in 2 cases. In kidney transplant recipients, vascular hepatic disease may be associated with high mortality, especially in major forms. Our findings indicate that peliosis hepatis may lead to severe fibrosing liver lesions. The course of vascular hepatic disease is not clearly modified by AZA withdrawal.
Adolescent↗
Absence of association between HLA antigens and chronicity of viral hepatitis in haemodialyzed patients.
The role of HLA antigens in the chronicity of viral hepatitis is still being debated. We analyzed the relation between HLA status and viral hepatitis in 558 consecutive haemodialyzed patients who underwent kidney transplantation. HLA A, B, DR status, ABO-Rh blood group, duration of haemodialysis, and number of blood units transfused during the dialysis period were known for all patients. Serological status for hepatitis B virus and hepatitis C virus and results of liver biopsies were available in 495, 300 and 316 patients, respectively. After correction for the number of tests performed, frequencies of HLA antigens did not differ significantly for: 1. hepatitis B virus infection (compared to HBsAg-positive and anti-HBc and/or anti-HBs-positive nonvaccinated patients); 2. hepatitis C virus infection (compared to anti-HCV-negative and -positive patients); 3. histopathological status (compared to patients who had chronic viral hepatitis and those who did not). These results suggest that there is no evidence for a significant role of a particular HLA antigen in the development of chronic viral hepatitis in haemodialysis patients with similar underlying immunosuppression and exposure to infection by hepatotropic viruses.
Adult↗
Perforin and granzyme B expression is associated with severe acute rejection. Evidence for in situ localization in alveolar lymphocytes of lung-transplanted patients.
To evaluate rejection episodes in lung-transplanted patients, we analyzed 31 bronchoalveolar lavage specimens for lymphocyte levels and lymphocyte expression of two intracytoplasmic activation markers, perforin, the pore-forming lytic protein, and granzyme B, a member of the serine esterase family. Using anti-human granzyme B and perforin mAbs, we show that their expression in alveolar lymphocytes is correlated with the severity of rejection as assessed by histological parameters and the patients' clinical status. The presence of these molecules may provide a prognostic parameter that will facilitate the patients' monitoring, particularly in cases with minimal acute lung rejection susceptible to rapid progression to severe rejection.
Biopsy↗
Influence of human immunodeficiency virus infection on hepatitis delta virus superinfection in chronic HBsAg carriers.
It is generally agreed that hepatitis B virus (HBV) replication is reduced by hepatitis delta virus infection (HDV) and augmented by human immunodeficiency virus (HIV) infection. However, the precise nature of the interactions between HBV, HDV and HIV is controversial. The aim of this study was to evaluate the impact of HIV infection on HBV and HDV replication, and on histological scores during delta virus superinfection in HDV-positive, chronic carriers of hepatitis B surface antigen (HBsAg). We studied 38 men and six women, 15 of whom were HIV-positive and all of whom had at least one marker of HDV infection. Serum hepatitis B e antigen (HBeAg), HBV DNA, HDV RNA, anti-delta antigen antibodies (anti-HD) IgM, anti-HD IgG and hepatitis delta antigen (HDAg) were tested for in the serum and liver, respectively; anti-hepatitis C virus (HCV) antibodies were detected using a second-generation recombinant immunoblot assay. Histological specimens were scored blindly according to Knodell's classification for periportal and intralobular necrosis, portal inflammation and fibrosis. HBV DNA was detected more frequently in the HIV-positive patients than in those who were HIV-negative (25 vs 0%; P = 0.01), while markers of HDV replication (serum anti-HD IgM, serum HDV RNA and liver HDAg) were as frequent in the HIV-positive patients (69%, 40% and 50%, respectively) as in those who were HIV-negative (75%, 52% and 30%, respectively; P > 0.05). By contrast, 31% of the HIV-positive patients were serum HDAg-positive compared to only 6% of the HIV-negative patients (P = 0.001). HDV antigenaemia and anti-HD antibodies usually fluctuated in the HIV-positive patients during follow-up. The mean Knodell score was similar in the HIV-positive (11.5 +/- 3.2) and HIV-negative (10.7 +/- 2) subgroups, as was the mean semi-quantitative index of hepatic necrosis, inflammation and fibrosis. Our results provide evidence that in HDV-positive patients: (1) HIV infection counters the inhibitory effect of HDV superinfection on HBV replication; (2) serum anti-HD IgM. HDV RNA and liver HDAg are not more frequent in HIV-positive than in HIV-negative patients, suggesting that HIV infection has no effect on HDV replication (although the significance of the increased frequency of HD antigenaemia remains unclear); (3) the histological severity of liver disease is not influenced by HIV status.
Adult↗
MR lymphography with superparamagnetic iron nanoparticles in rats: pathologic basis for contrast enhancement.
OBJECTIVE: The purpose of this study in rodents was to determine the pathologic basis for enhancement patterns of hyperplastic and tumours lymph nodes shown by MR lymphography after IV injection of superparamagnetic iron oxide nanoparticles (AMI-227). MATERIALS AND METHODS: Hyperplastic and tumorous lymph nodes were imaged in vivo at 1.5 T 1 day after IV administration of AMI-227 (40-200 mumol Fe/kg) to rats. Inguinal and axillary lymph nodes were surgically resected, and in vitro imaging was done by using the same magnet with a prototype coil that allowed a pixel size of 70 x 230 microns. Imaging findings were correlated with histologic findings and iron staining of the nodes. RESULTS: With all sequences, at doses of 80 mumol Fe/kg or higher, the signal intensity of hyperplastic nodes was lower than on unenhanced images. The same pattern was seen in the remaining normal tissue of tumourous lymph nodes. This T2* effect was a result of clustered particles inside macrophages in the lymphatic sinuses. At doses of 200 mumol/kg, the tumor itself consistently showed an increase in signal intensity on T1-weighted images. This T1 effect probably resulted from particles leaking into the interstitial spaces of the tumor. CONCLUSION: After IV injection of superparamagnetic nanoparticles, a decrease in signal intensity indicates active uptake of particles into macrophages, whereas an increase in signal intensity indicates altered capillary permeability in tumor. These findings in rats may prove to be clinically useful in the future for differentiating benign from malignant enlarged lymph nodes.
Animals↗
A highly unusual combination of pulmonary pathogens in an HIV infected patient.
We report on a case with an unusual combination of pulmonary pathogens including Pneumocystis carinii, Rhodococcus equi and Toxoplasma gondii in an HIV infected patient. The multiple microbiological procedures required to ascertain the etiological diagnoses of pneumonitis in HIV-seropositive subjects are discussed.
AIDS-Related Opportunistic Infections↗
Effectiveness of adenine arabinoside 5'-monophosphate in kidney transplant recipients with chronic active hepatitis B.
Hepatitis B virus infection is responsible for both morbidity and mortality in kidney transplant recipients. Adenine arabinoside 5'-monophosphate (ARA-AMP), a synthetic purine nucleotide with anti-viral activity, leads to a sustained interruption of HBV replication in approximately 40% of immunocompetent patients. We report the results of a pilot study using ARA-AMP to treat HBV-related chronic active hepatitis in kidney transplant recipients. Ten patients (2 females and 8 males, mean age 44 years, mean time post-transplantation 163 months) received a 28-day course of ARA-AMP intramuscularly: 5 mg/kg twice daily for the first 5 days during hospitalization and subsequently 5 mg/kg once daily at home for the remaining 23 days. Mean follow-up was 18 months, ranging from 7 to 28 months. All patients but one had biopsy-proven chronic hepatitis, including five cases of cirrhosis. All patients had been chronic HBs Ag carriers for more than 1 year and had active replication as assessed by the presence of serum HBV DNA (mean titre, 270 pg/ml, ranging from 12 to 997 pg/ml, Genostics method). HBe Ag was present in 7 of the 10 patients. Pretreatment creatinine was normal. In four of the 10 patients, HBV DNA became undetectable respectively 1, 1, 5, and 11 months after beginning ARA-AMP. In five patients, HBV DNA decreased during ARA-AMP therapy but subsequently increased although no change was noted during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Fatal cyclophosphamide-induced interstitial pneumonitis in a renal transplant patient.
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Biopsy↗