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Biomedical subjects

B N Pham

Publications and source records attributed to B N Pham.

At least 19 recordsLinked to original sources
PubMed1999

Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men.

The aim of this study was to assess the influence of human immunodeficiency virus (HIV) infection on chronic hepatitis B. In a series of 132 (65 anti-HIV positive) homosexual non-drug addicted men with chronic hepatitis B, the liver function was assessed with biochemical tests; the degree of hepatitis B virus (HBV) replication was assessed with serum HBV DNA level and with immunoperoxidase staining of hepatitis B core (HBc) antigen on liver specimens; and the severity of liver lesions was assessed with an histology activity index. Anti-HIV-positive and anti-HIV-negative patients were not different for serum aspartate transaminase activity, bilirubin, prothrombin, and histology activity index. Anti-HIV-positive patients had lower serum alanine transaminase activity levels (P =.0001), lower serum albumin levels (P =.0009), and higher serum HBV DNA levels (P =.01). There was a higher prevalence of cirrhosis in anti-HIV-positive patients (P =.04). In homosexual men with chronic hepatitis B, HIV infection is associated with a higher level of HBV replication and a higher risk for cirrhosis without increased liver necrotico-inflammatory process.

Alanine Transaminase↗
PubMed1998

Relationship between the effector T-cell response and viremia in symptomatic chronic hepatitis C.

OBJECTIVE: The purpose of this study was to assess the relationship between hepatitis C virus (HCV) viremia, HCV genotype, histologic activity index, and intrahepatic densities of immunocompetent lymphoid cells in chronic hepatitis C. METHOD: Liver biopsy specimens from patients with chronic hepatitis and anti-HCV antibodies, 5 with low-level HCV viremia and 26 with high-level HCV viremia, were studied. Sections of snap-frozen specimens were immunostained with monoclonal antibodies directed against different subsets of B cells, follicular reticulum cells, and T cells, including CD45RA-naive cells and CD45RO-primed cells. The densities of each subset of lymphoid cells were calculated with a computerized image analyzer. Hepatitis C virus RNA was measured with a quantitative branched DNA signal amplification assay, and HCV genotypes were determined with the line probe assay. RESULTS: A statistical correlation was found between the level of HCV viremia and the histologic activity index (P = .002). There were also significant correlations between the densities of CD3+ T cells and CD45RO+-primed cells in the liver and the histologic activity index and (P = .024 and P = .005, respectively), and significant correlations were found between the densities of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD45RO+-primed cells and HCV viremia (P = .005, P = .03, P = .03, and P = .02, respectively). Whatever the viremia status, CD45RO-primed cells were more numerous than CD45RA-naive cells in lobules and portal tracts. The CD45RO/CD45RA ratio was significantly higher when intraportal lymphoid aggregates were present. Eight patients were infected with genotype 1b, and 11 were infected with genotype 3b. There were no statistical differences in the histologic activity index, viremia, and density of immunocompetent cells in the liver between these two HCV genotypes. CONCLUSIONS: The results of this study suggest that the density of antigen-primed effector T cells in the liver of symptomatic patients with chronic hepatitis C is adapted to HCV viremia but is independent of the occurrence of genotypes 1b or 3a, the most frequent genotypes found in France.

Adult↗
PubMed1997

Acute hepatitis caused by alverine associated with anti-lamin A and C autoantibodies.

We report the case of a 67-year-old woman in whom onset and regression of acute hepatitis were closely related to the time of administration and withdrawal of the smooth muscle relaxant alverine. Antinuclear antibodies were positive, and their titer followed the course of hepatitis. They presented a smooth rim-like nuclear immunofluorescence staining pattern. Immunoblot assay showed that they were directed against lamin A and lamin C. This suggests that alverine should be added to the list of drugs known to produce acute hepatitis, and that drug-induced liver injury is a possible cause of antinuclear antibodies specific for lamin A and lamin C.

Acute Disease↗
PubMed1997

Complement activation after ischemia-reperfusion in human liver allografts: incidence and pathophysiological relevance.

BACKGROUND & AIMS: Little is known about the occurrence and possible consequences of local complement activation in human liver transplantation. The aim of this study was to search for signs of complement activation in human liver allografts and evaluate their relationship to cell injury and leukocyte sequestration. METHODS: In 33 postreperfusion biopsy specimens, 9 preoperative specimens, and 10 intraoperative specimens, the cytolytic membrane attack complex of complement was localized, expression of complement inhibitors was evaluated, and intragraft accumulation of leukocytes and platelets was quantitated. RESULTS: In control samples and preoperative biopsy specimens, the membrane attack complex was detected only in extracellular deposits, associated with its soluble inhibitors clusterin and vitronectin. Comparable observations were performed in 14 postoperative specimens. In the remaining 19 postoperative specimens, membrane attack complex decorated a variable proportion of hepatocytes. The extent of membrane attack complex deposition correlated with the increase in postoperative aspartate aminotransferase levels in serum (P = 0.002) and the decrease in postoperative factor V levels in serum (P = 0.002). It also correlated with the number of leukocytes and platelets accumulating within the graft (P < or = 0.001). CONCLUSIONS: Local complement activation is frequent during human liver transplantation and probably contributes to cell injury and leukocyte sequestration in the allograft.

Adult↗
PubMed1996

Restriction of V beta gene usage of liver-derived lymphocytes in chronic hepatitis B and C.

T lymphocytes have been reported to be the predominant inflammatory cells in the liver of patients with chronic viral hepatitis. Their presence may reflect either nonspecific inflammation or a virus-specific immune response. To assess the repertoire of intra-hepatic T cells, we investigated the TCR V beta gene usage of T cells in 10 patients with chronic hepatitis B and 15 with chronic hepatitis C. Liver-derived lymphocytes and peripheral blood lymphocytes were analyzed by flow cytometry. Five out of the 10 hepatitis B patients were found to have an accumulation of certain V beta T cells in the liver (V beta 6.7; V beta 6.7; V beta 3.1, V beta 5.1, and V beta 6.7; V beta 3.1; V beta 12.1, respectively). Four out of the 15 hepatitis C patients were found to have an accumulation of certain V beta T cells in the liver (V beta 5.1; V beta 8 and V beta 5.2 and 5.3; V beta 3.1 and V beta 5.2 and 5.3; V beta 3.1 and V beta 12.1, respectively). Despite a limited screening of V beta subfamilies, this study indicates that, in patients with chronic hepatitis B and C, T cells using a certain V beta gene may accumulate in the liver. This suggests that intra-hepatic T cells are oligoclonal and possibly virus specific. Our results argue against the role of a superantigen in perpetuating liver disease. In addition, this study supports a role for T lymphocytes in the pathogenesis of chronic hepatitis C.

Adult↗
PubMed1996

Relationship between composition of lymphoid cell infiltrates in the liver and replication status in chronic hepatitis B: an immunohistochemical study.

The purpose of this in situ immunophenotyping study was to assess the nature of lymphoid cells involved in chronic hepatitis B with various levels of replication. Replicative status was studied in 25 patients with chronic hepatitis B. Different subsets of T cells, B cells, natural killer cells, and follicular dendritic cells were counted with a computerized image analyzer. Twelve patients had chronic hepatitis B with a high level of replication, nine without replication, and four with a low level of replication. The number of CD3+ T cells was significantly higher in the liver of patients with replication. In all cases, CD8+ T cells were the most numerous cells in the lobules and CD4+ T cells were the most numerous cells in the portal tract. Intra-portal lymphoid follicles were observed in 33% of patients with a high level of replication. The CD57+ natural killer cells were more numerous in patients with a low level of replication. This study suggests that in immunocompetent patients, the intensity and type of hepatic immune response are directly determined by the HBV replication.

Adult↗
PubMed1995

Immunostaining for membrane attack complex of complement is related to cell necrosis in fulminant and acute hepatitis.

BACKGROUND/AIMS: Complement activation is one of the mechanisms involved in inflammatory lesions. Initiation of the complement terminal pathway at a cell surface leads to the formation of a cytolytic membrane attack complex. Our study assess whether a membrane attack complex-associated mechanism is involved in liver cell necrosis of fulminant and subfulminant hepatitis. METHODS: Immunostaining for membrane attack complex was compared with immunostaining for cytokeratin and complement inhibitory proteins such as membrane cofactor protein, decay-accelerating factor, and homologous restriction factor in 15 patients with fulminant hepatitis and 5 patients with nonfulminant acute hepatitis. RESULTS: In all patients, hepatocytes surrounding necrotic areas, but not those at a distance, were stained for membrane attack complex, whereas the opposite staining pattern for membrane cofactor protein was observed. In controls, no hepatocyte staining for membrane attack complex was observed, whereas membrane cofactor protein, but not decay-accelerating factor or homologous restriction factor, was detected on hepatocytes. CONCLUSIONS: Complement activation by antibody-dependent or non-antibody-dependent mechanisms might be involved in the pathogenesis of either fulminant or acute hepatitis. Modulation of membrane cofactor protein expression on hepatocytes might contribute to the sensitivity of hepatocytes to membrane attack complex and subsequent cell lysis.

Acute Disease↗
PubMed1995

CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia and not to hepatitis C virus genotypes in chronic hepatitis C.

The pathogenic mechanisms that lead to chronic hepatitis C are unknown. As hepatitis C virus (HCV) has been shown to induce T cell response, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver of patients with chronic hepatitis C in relation to viraemia or HCV genotypes. The immunophenotypes of liver-derived lymphocytes were analysed in 26 patients by flow cytometry and immunohistochemistry. Viraemia was quantified by branched DNA assay. Using this assay, HCV RNA was not detectable in six patients. HCV RNA was detected in 20 patients, and titres ranged from 8 to 137 x 10(6) Eq/ml. Genotyping was performed using a line probe assay. Type 1a, 1b, 2a, 3a and 4a were found to infect 2, 10, 2, 7 and 3 patients, respectively. The CD4+/CD8+ ratio of liver-derived lymphocytes was significantly higher (P < 0.01) in patients with detectable viraemia than in patients without detectable viraemia. In contrast, neither the percentage of gamma/delta T lymphocytes nor that of CD2+CD57+ cells was different in the groups. When comparing the CD4+/CD8+ ratio, the percentage of gamma/delta T lymphocytes or CD2+CD57+ cells according to genotype, the differences were not significant. These results suggest that the CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia but not to HCV genotypes in patients with chronic hepatitis C, and that T lymphocytes may be involved in the pathogenesis of liver lesions in chronic hepatitis C.

Adult↗
PubMed1994

Etiology of chronic hepatitis in France: predominant role of hepatitis C virus.

The aim of this study was to assess the causes of histologically proven chronic hepatitis in a series of 357 consecutively admitted patients. Patients with chronic alcohol intake above 50 g per day, Wilson's disease, idiopathic hemochromatosis or homozygous alpha-1 antitrypsin deficiency were excluded. Sera of all patients were tested for antibodies to hepatitis C virus with second-generation enzyme-linked immunoassay and recombinant immunoblot assay, for markers of hepatitis B and hepatitis D viruses, and for autoantibodies. Detection of hepatitis C viral RNA by polymerase chain reaction was attempted if recombinant immunoblot assay was indeterminate, or if both viral and autoimmune markers were absent. If no serum markers, including HCV RNA, were found, the cause of chronic hepatitis was considered as unknown. The cause of chronic hepatitis was found in 343 cases (96.4%), including three patients with HCV RNA as the only marker. Chronic hepatitis was related to hepatitis C virus in 51.8%, to hepatitis B virus in 32.8% (including hepatitis D infection in 3.1%), and to autoimmune hepatitis in 5.9% of cases, respectively. No case of drug-induced chronic hepatitis was observed in this series, and in 5.9% of cases, there were probably multiple causes. Finally, in 3.6% of the cases the cause of chronic hepatitis remained unknown despite extensive evaluation suggesting the existence of a non-A, non-B, non-C viral agent.

Adult↗
PubMed1994

Flow cytometry CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication in chronic hepatitis B.

T lymphocytes have been assumed to play an essential role in tissue injury in patients with chronic hepatitis B. As hepatitis B virus (HBV) is considered as a major factor controlling liver inflammation, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver in accordance with viral replication. Liver-derived lymphocytes and peripheral blood lymphocytes were analysed by flow cytometry in 21 patients with histologically confirmed chronic hepatitis B without cirrhosis. Viral replication was quantified by hybridization of serum HBV DNA. Eleven patients exhibited an active viral replication with serum HBV DNA ranging from 10 to 388 pg/ml at the time of the liver biopsy, whereas 10 patients had no detectable serum HBV DNA. In patients exhibiting viral replication, CD4+/CD8+ ratios of liver-derived lymphocytes were significantly higher (P < 0.05) than those obtained in patients without viral replication. In contrast, the percentage of T cells expressing the gamma/delta receptor and that of CD2+/CD57+ cells were similar in both groups of patients. Furthermore, in patients exhibiting viral replication, CD4+CD8+ ratios of liver-derived lymphocytes correlated with serum HBV DNA levels (P < 0.001). No relationship between CD4+/CD8+ ratio of liver-derived and peripheral blood lymphocytes was observed. Our data indicate that, in patients with chronic hepatitis B, the CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication. This suggests that in situ helper/inducer CD4+ T lymphocytes may positively regulate the cytotoxic T cell activity in patients with HBV-related chronic hepatitis.

Adult↗
PubMed1993

Cryoglobulinemia with vasculitis associated with hepatitis C virus infection.

Essential mixed cryoglobulinemia is frequently associated with chronic hepatitis. This report presents four cases of cryoglobulinemia with vasculitis associated with chronic hepatitis related to hepatitis C virus infection. Hepatitis C virus infection was ascertained in the four patients by both the presence in the serum of anti-HCV antibodies detected by the four-antigen recombinant immunoblot assay and of HCV RNA detected by polymerase chain reaction. In two patients tested, anti-HCV antibodies were not detected after centrifugation in the purified cryoglobulin but were detected in the supernatant. HCV RNA was detected in the purified cryoglobulin in all four patients and was detected in the supernatant in three patients. In one patient receiving recombinant interferon alfa, serum aminotransferases normalized and cryoglobulin disappeared; in another patient receiving recombinant interferon alfa, serum aminotransferases remained high and the cryoglobulin persisted. The presence of HCV RNA in the cryoglobulin and the parallelism of the changes of the cryoglobulinemia and of the serum aminotransferases during recombinant interferon alfa administration suggest that HCV infection is responsible for the production of cryoglobulinemia and vasculitis. It is proposed that HCV infection is a cause of cryoglobulinemia associated with chronic hepatitis.

Adult↗
PubMed1993

Hepatitis C virus infection in anti-HIV positive and negative French homosexual men with chronic hepatitis: comparison of second- and third-generation anti-HCV testing.

To determine the prevalence of hepatitis C virus (HCV) infection in homosexuals with chronic hepatitis, we tested for anti-HCV antibodies 113 (47 anti-HIV positive) French non-drug-addicted homosexual men admitted for chronic viral hepatitis. Anti-HCV were detected with second- and third-generation ELISAs (ELISA2 and ELISA3) and RIBAs (RIBA2 and RIBA3). Chronic hepatitis was related to non-A, non-B infection in four, to hepatitis D virus (HDV) infection in five and to hepatitis B virus (HBV) infection in 104 patients. Anti-HCV positivity was found in 50.4% and 12.4% of the 113 patients, with ELISA2 and ELISA3, respectively. Positivity with RIBA2 and RIBA3 was found in only six of the 57 ELISA2 positive patients (all six were ELISA3 positive). The high prevalence of positivity with ELISA2 not confirmed by RIBA2 or RIBA3 suggests false-positive results. ELISA2 positive results were more frequent with frozen serum samples than with fresh serum samples (62% vs 23.5%, p = 0.0003). However, even with fresh serum, ELISA2-positive RIBA-negative results remained frequent in anti-HIV positive patients. ELISA3 seems to give more specific results. We conclude that the prevalence of HCV infection, as assessed with RIBA, was 5.3% among French homosexual men with chronic hepatitis (3.8% after exclusion of transfused patients). This low prevalence suggests that homosexual transmission of HCV is relatively uncommon.

Adult↗
PubMed1991

Trypanosoma cruzi: infection of T lymphocytes and their destruction by antibody-dependent cell-mediated cytotoxicity.

We have demonstrated, with optical and transmission electron microscopy, that Trypanosoma cruzi trypomastigotes infect and multiply inside T lymphocytes. The infection rate we have observed in T cells was similar to that seen in the case of macrophage or polymorphonuclear cell infection. Flow cytofluorometric analysis of T lymphocytes purified from mice in the acute phase of the disease, revealed the presence of parasite-derived antigens on their surface. These antigens appear to be specific to T. cruzi and they could be the result of intracellular parasite antigens as well as adsorption of T. cruzi antigens on the surface of noninfected T cells. Antibodies recognizing these surface antigens were present in both T. cruzi-infected mouse and human sera. They were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of nonimmune mononuclear cells both in autologous and in heterologous combinations. Consequently, we provided evidence suggesting that T lymphocytes could be destroyed during the acute phase of Chagas' disease either by cell infection or by an ADCC mechanism against cells bearing parasite antigens on their surface. Thus, the ability of trypomastigotes to invade T cells may play a crucial role in the immunopathogenesis characteristic of Chagas' disease.

Animals↗
PubMed1989

T lymphocyte activation in systemic lupus erythematosus analysed by proliferative response to nucleoplasmic proteins on nitrocellulose immunoblots.

Polyclonal B cell activity in systemic lupus erythematosus (SLE) may be under T cell control. The use of nitrocellulose immunoblots for the analysis of recognition by peripheral blood lymphocytes of nucleoplasmic proteins in SLE patients led to the characterization of significant proliferative responses to 68K (U1 RNP); SS-B; B-B' and D (Sm) antigen in 15 of 20 patients. Variations of proliferative response were parallel to disease activity over a follow-up period of greater than or equal to 6 months, conferring some prognostic value to the assay of lymphocyte response to nucleoplasmic antigens. The pattern of reactivity differs from the corresponding serum antibody profile, and purified T cell suspensions (greater than 95% pure) were shown to proliferate in response to soluble nucleoplasmic antigens, indicating that T and B cell repertoires against nucleoplasmic proteins may differ. This suggests that activated helper T cells contribute to the fine modulation of B cell reactivity to subcellular particles to determine the particular antibody profile of the patients.

Adolescent↗