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Dear Editor, Chronic spontaneous urticaria (CSU) is an inflammatory disease characterized by spontaneous weals or angio-oedema for more than 6 weeks. International guidelines from the EAACI/GA SP 2 sp LEN/EDF/UNEV were published in 2018,1 but practice remains heterogeneous, especially for CSU refractory to H SB 1 sb antihistamines and regarding states' official drug approval and reimbursement policies. 3 (iii) The working group does not recommend the adjunction of H SB 2 sb antihistamines or montelukast to H SB 1 sb antihistamines in CSU, owing to the lack of demonstrated efficacy. [Extracted from the article]

Our objective was to evaluate performance of the clinical laboratories for the detection of antinuclear antibodies (ANA) by using indirect immunofluorescence method (IIF), in France. A national external quality assessment (EQA) on ANA detection was organized by the French health products safety agency once a year since 1998. Between 606 to 687 laboratories together with six university reference laboratories experienced in performing tests in autoimmunity participated in the six-year consecutive survey. Each laboratory had to answer to methodological procedures and give coded responses. Variability in IIF methodological procedure was observed. Use of inappropriate microscope magnifications for reading slides or nonconventional cutoff dilution of serum were pointed out to concerned laboratories. Concerning ANA measurement, the rate of good responses ranged from 92.7% to 99.5% of the laboratories when the samples contained ANA. A wide dispersion of ANA titers obtained on a same sample was repeatly observed every year. Misinterpretation of particular fluorescence pattern was noticed. On ANA negative sample, the rate of good responses was 94.3%. In conclusion, ANA detection in routine practice is far from being standardized. However, EQA may have an impact on ANA detection performance when it is conducted on several consecutive year surveys, by providing advice for participating laboratories to limit inter laboratory variations related to methodological procedures. [ABSTRACT FROM AUTHOR]

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 × 106 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 γ/δ T lymphocytes nor that of CD2+CD57+ cells was different in the groups. When comparing the CD4+/CD8+ ratio, the percentage of γ/δ 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. [ABSTRACT FROM AUTHOR]

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/mI 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 γ/δ 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 cytoxic T cell activity in patients with HBV-related chronic hepatitis. [ABSTRACT FROM AUTHOR]

Polyclonal B cell activity in systemic lupus erythematosus (SLE)may be under T cell control. The use of nitrocellulose irnmunoblots 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 (UI 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 &ges; 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 ( >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. [ABSTRACT FROM AUTHOR]

Introduction: Deformities of the spine and thorax in adolescent idiopathic scoliosis affect appearance. They are a cause of inferiority, affecting psychological well-being and the social life of the patients. To contribute to curve evaluation, planning in curve correction, and improving the post-operative aesthetics, many studies on the correlation between appearance and radiography in the assessment of shoulder and neck balance have been reported recently. In general, these studies did not clarify which indices are required to evaluate shoulder and neck balance. This study aimed to learn about indices to assess shoulder and neck balance in adolescent idiopathic scoliosis in correlation between clinical appearance and radiography., Materials and Methods: This observational study recruited 50 patients with adolescent idiopathic scoliosis who were 12 to 18 years of age with Cobb angle >10°. Based on Pearson correlation coefficient, radiographic parameters such as coracoid height difference (CHD), clavicle rib intersection distance (CRID), clavicle angle (CA), clavicle chest cage angle difference (CCAD), and T1 tilt angle were evaluated in correlation with clinical shoulder and neck balance by difference of inner shoulder height (SHi), difference of outer shoulder height (SHo), and neck tilt angle., Results: SHi was moderately correlated with T1 tilt angle (r [hereafter] = 0.45), CA (0.47), and CHD (0.57), high-moderately correlated with CRID (0.64), very-highly correlated with CCAD (0.84). SHo was moderately correlated with T1 tilt angle (0.43), highly correlated with CHD (0.60), CA (0.63), and CRID (0.72), and very-highly correlated with CCAD (0.89). T1 tilt angle was high-moderately correlated with neck tilt angle (0.76). The correlation coefficients between clinical and radiographic shoulder and neck balance according to sex, BMI, type of main curve, severity of main curve did not change significantly., Conclusion: There was a very high correlation between SHo (shoulder tilt) and CCAD (0.89); the correlation between SHo and CRID was high-moderate (0.72), but CRID is easier than CCAD to evaluate on radiographs. On the other hand, T1 tilt angle, which is the easiest radiographic parameter to evaluate, had a high-moderate correlation with neck tilt angle (0.76) but a moderate correlation with SHo (0.43)., Competing Interests: The authors declare no potential conflict of interest., (© 2024 Malaysian Orthopaedic Association (MOA). All Rights Reserved.)

Objectives: report on acceptance of voluntary interruption of pregnancy in 2021 in the French 18-to-24-year-old population and to compare the results with the acceptance reported in 2014 in the Institut Français d'Opinion Publique survey., Methods: A French cross-sectional study with questionnaires administered between February and April 2021. The target population was 18 to 24 years of age. For purposes of comparison, the question on acceptance of voluntary interruption of pregnancy was basically the same as that of the 2014 Institut Français d'Opinion Publique survey, as were the proposed response modalities. Data were described in terms of means ± standard deviation and number (percentage). Conditions for acceptance of voluntary interruption of pregnancy were compared with the results of the 2014 Institut Français d'Opinion Publique survey using the Chi-square test. Factors associated with acceptance of voluntary interruption of pregnancy without restrictive conditions were studied using univariate analysis (Student, Chi-square or Fisher exact tests) and multivariate analysis (logistic regression)., Results: Close to 2000 (1936) questionnaires were completed, including 1225 among 18-to-24-year-olds. Voluntary interruption of pregnancy was accepted without restrictive conditions by 92.1% of the study population (95%CI: 90.4-93.5) compared to 79.0% in 2014 (p < 0.0001). Female gender (93.4 % versus 85.8%; OR = 2.1 [1.4-3.4]; p = 0.0009) and residence outside of Paris (94.9% versus 86.6%; OR = 2.8 [1.9-4.3]; p < 0.0001) were significantly associated with acceptance of voluntary interruption of pregnancy without restrictive conditions., Conclusion: In 2021 in France, the 18-to-24-year-old population is massively favorable to voluntary interruption of pregnancy without restrictive conditions, in a significantly higher proportion than in 2014., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent ne pas avoir de liens d'intérêts., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Systemic sclerosis is a rare connective tissue disease characterized by skin and several internal organ fibrosis, systemic vasculopathy and immune abnormalities. Even if fibroblasts and endothelial cells dysfunction, as well as lymphocytes and other immune cells implication are now well described, the exact origin and chronology of the disease pathogenesis remain unclear. Oxidative stress, influenced by genetic and environmental factors, seems to play a key role. Indeed, it seems to be implicated in the early phases of fibrosis development, vasculopathy and in immune tolerance abnormalities shared by all patients, although disease expression is heterogeneous. To date, no curative treatment is available. Even if immunosuppressive treatment or drugs acting on vascular system are proposed for some patients, overall, treatment efficiency remains modest. Only autologous hematopoietic stem cells transplantation, reserved for patients with severe or rapidly progressive fibrosis, has recently demonstrated efficiency, with lasting regression of fibrosis. Nevertheless, this treatment can expose to important, life-threatening toxicity. In the last decade, new mechanisms implicated in the pathogenesis of systemic sclerosis have been unraveled, bringing new therapeutic opportunities. In this review, we offer to focus on recent insights in the knowledge of systemic sclerosis pathogenesis and its implication in current and future medical care., (Copyright © 2019 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Red blood cell allo-immunization is the immune response of an individual to foreign red blood cell antigens not present on the surface of their own cells. The aim of that paper is to clarify the different factors influencing the antibody response against red blood cell antigens., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

We report a case of a potential drug-drug interaction in a woman treated by a first injection of high-dose methotrexate for a T-lymphoblastic lymphoma. Valaciclovir, fluoxetine and pantoprazole were given concomitantly. A methotrexate overdosage was shown at 36 h after infusion associated with a severe renal failure. Alkaline hyperhydration, folinic acid and carboxypeptidase G2 were given. Prescription analyses by pharmacists and literature research have permitted us to suggest that a drug-drug interaction between methotrexate and proton pump inhibitors (PPI) was responsible for this renal failure. Several mechanisms of interaction were suggested and might be related to the inhibition of renal methotrexate transporters by PPI, an increase in the methotrexate efflux to the blood by an upregulation of multidrug resistance protein 3 by PPI or genetic polymorphisms. This case shows that pharmacists can help physicians to optimize patient treatment: they consensually decided on the systematic discontinuation of PPI or a switch to ranitidine when patients were treated by high-dose methotrexate., (Copyright © 2011 S. Karger AG, Basel.)

Since the discovery of blood groups in humans, several hundred new red blood cell antigens have been identified. Multiple terminology modes have been used to denote each new antigen identified, but without any consistent rules, nor international consensus. This was largely due to the many discoverers of these antigens, using either letters of the alphabet, numbers, part of the patient or donor's name, place of discovery or animal names. Besides, alternative terminologies for the Rh system were implemented in the middle of the twentieth century (Rosenfield, Fisher-Race, Wiener). The International Society of Blood Transfusion described for the first time in 1980 the advantages of an alphanumeric and homogeneous nomenclature, keeping with the genetic bases of blood groups, as well as a classification of all RBC antigens within several families. A variant of this new terminology, exclusively numerical, was simultaneously established, mainly designed for computer data exchange. Nearly 30 years later, 308 red blood cell antigens are described within 30 systems, 12 collections, one 700 series and one 901 series of blood groups. Any person involved in the field of immuno-haematology must master both the usual and international nomenclatures. The Wiener nomenclature used for Rh haplotypes, still largely used today, is also important to be known. The systematic use of the international nomenclature should be strongly encouraged, either in the labelling of blood products, clinical laboratory reports or blood type cards.

Aim of the Study: Determination of blood group antigens from data obtained by using molecular methods (genotyping) has become an indispensable tool in the specialized immunohematology laboratories. The French National Reference Centre for Blood group typing (CNRGS) routinely performs genotyping of the FY, JK and MNS system (common genotyping), providing a phenotype deduced from genotyping data for FY1, FY2, JK1, JK2, MNS3 and MNS4 antigens., Patients and Methods: We performed a study to evaluate the common genotyping prescriptions referred to the CNRGS over the last three years., Results: Between February 2006 and February 2009, the CNRGS performed 2392 genotyping, including 981 common genotyping. Analysis of 172 common genotyping performed in 2008 showed that 63.8% of the prescriptions expressed a genotyping demand. Of the latter, 42.7% were genotyping prescriptions only, whereas 57.2% were prescriptions of genotyping associated with alloantibody identification. All prescriptions refer to blood group genotyping indications issued from guidelines, with no incorrect prescription, that are patients transfused within four months before blood sampling in 63.6% of cases or a positive direct antiglobulin test in 24.5% of cases. Lastly, 36% of the blood samples referred to the CNRGS had no genotyping prescription. Yet, common genotyping was performed by the CNRGS to get complete immunohematology data for antibody identification., Conclusion: Usefulness of blood group genotyping in specialized immunohematology laboratories is obvious. However, the strategy for implementation of molecular methods remains to be defined. Use of high-throughput DNA analysis should change our way of working.

The technology allowing freezing of RBC units has been available for many decades. The high-glycerol method for RBC storage at -8 degrees C is predominantly used. Several studies have shown satisfactory results regarding the in vitro viability and function of cryopreserved RBCs. RBC freezing is nowadays mostly encountered in rare blood programs and military deployments. Preservation time of frozen RBCs appears to be virtually indefinite, but most countries apply a 10-year outdate. There is no mandatory time restriction in France. The National Rare Blood Bank currently includes 962 (17.5%) RBC units aged to years or more and 153 (2.8%) aged 20 years or more. Since 1994, 1957 RBC units have been thawed and transfused, among which 118 were aged 10 years or more and 8 were aged 20 years or more. Discarding RBC units older than to years may be highly sensitive for very rare blood groups, e.g., U-, of which approximately 30 percent of the cryopreserved units are aged to years or more. However, the lack of nucleic acid testing for HIV and HCV may be problematic for old RBC units drawn from donors who were not subsequently tested for these markers, which is now mandatory in most countries. Regarding the 118 transfused RBC units older than 10 years, no evidence of hemolysis of thawed RBCs and no transfusion reaction, clinical or biologic hemolysis, or transfusion ineffectiveness was reported, either by any of the parties involved in the transfusion supply of rare RBC units or through the French hemovigilance program, which requires a mandatory report of any transfusion reaction. It has recently been suggested to extend the 10-year restriction in some countries. Considering our experience and observational data, we may consider it safe and efficient to transfuse rare frozen RBC units older than 10 years. An international consensus for RBC cryopreservation time should ideally be established.

A rare blood group is usually defined as the absence of a high prevalence antigen or the absence of several antigens within a single blood group system, if its prevalence in France is 4/1000 or less in the general population. An individual with a rare blood phenotype can develop a naturally-occurring or immune antibody corresponding to his rare specificity. In case an extremely low stock of compatible blood is available at the national level, a so-called "transfusion deadlock" is described. Most of the individuals with a rare blood group are coincidently identified when a routine pretransfusion testing or pregnancy follow-up is performed, if the antibody(ies) corresponding to the rare specificity is(are) present. Other individuals are discovered following a systematic red cell typing, or family investigations in siblings. One hundred and twenty-one rare blood specificities and 42 rare blood genotypes are currently defined at the French National Reference Laboratory for Blood Groups (CNRGS-Paris). The French national registry of individuals with a rare blood phenotype/genotype includes about 9600 people, who are urged to regularly donate blood for the National Rare Blood Bank. This bank, based on a homologous blood transfusion program, is in charge of the long-term storage of rare frozen blood units, that can only be delivered after receiving authorization from the CNRGS. The global and individual care management of the individuals with a rare blood group, concerning potentially several hundred thousand people in France, requires a close cooperation between all the protagonists within the transfusion chain.

The French Health Products Safety Agency organized in 2005, for the scheme of the national external quality assessment, a survey on antibodies against thyroid constituents which included for the first time the quantitative assay. The purpose of this survey was to assess the quality of the different methods of these assays. The overall qualitative results are satisfactory. However, this survey pointed out a lower performance for immunodot which appeared to have been misused. Concerning the titer of antibodies, results show a broad dispersion between reagents. This confirms the lack of a real standardisation despite of the existence of the international MRC standards.

In 2003, for the scheme of the French national external quality assessment, Afssaps organized for the first time a survey on auto-antibodies detected on liver, kidney and stomach tissues. This survey had two purposes: first to make an inventory of the methodology applied by the medical laboratories and secondly to assess the quality of the results. The survey sample contained M2 anti-mitochondrial antibodies. Overall results are satisfactory. Concerning the titer of antibodies, a broad dispersion of results was observed (12% of titers were upper than the expected titer). Delivered information to the participants, at the end of the survey, should improve analytical procedures applied by the biologists. An effort of standardization by using titrated internal controls would be suitable.

In 2003, for the scheme of the French national external quality assessment, Afssaps sent to medical laboratories a sample for which two analyses could be carried out: the electrophoresis of proteins and the characterization for monoclonal immunoglobulin. The purpose of this new approach was to make it possible to the laboratories to transpose their usual diagnostic reasoning. This survey recalled to the biologists that it is necessary to check the sensitivity of the test of electrophoresis of proteins used in first intention and to use advisedly the anti-serums anti-free chains. Moreover this operation reinforced the educational aspect of the external quality assessment, pointing out the importance to ensure the coherence of the results of these two analyses carried out with a same diagnostic aim.

A significant proportion of patients with detectable antibodies to hepatitis C virus have normal serum alanine transaminase levels. Our aim was to study the outcome of this group. Between 1992 and 1999, 135 consecutive anti-HCV-positive patients with persistently normal ALT were followed for 3.6 +/- 2.3 years (0.5 to 8.5 years), 108 had a liver biopsy at inclusion, and 24 had a second liver biopsy 3.5 +/- 1.0 years later. Serum HCV RNA was detectable with PCR in 94 patients (69%) and not detectable in 41 patients (31%). Patients with and without detectable serum HCV RNA had similar epidemiological characteristics. Serum ALT levels and anti-HCV ratio were lower (P =.001), and histological lesions had lower grade and stage in patients without detectable serum HCV RNA (P =.001). Liver HCV RNA was not detectable with PCR in the 12-serum HCV RNA-negative patients tested. During follow-up, all patients without detectable serum HCV RNA remained HCV RNA-negative and kept normal serum ALT; all patients with detectable serum HCV RNA remained HCV RNA-positive, 20 (21%) had a slight fluctuation of serum ALT above the upper limit of normal. No significant changes were observed in the liver lesions of the 24 patients who underwent a second liver biopsy. In anti-HCV-positive patients with persistently normal serum ALT, histological lesions are significantly lower in HCV RNA-negative than in HCV RNA-positive patients. During follow-up, the HCV RNA status of patients remained unchanged; 21% of the patients with detectable serum HCV RNA had slight increase in serum ALT levels, but histological lesions remained stable.

Background: Drug-induced liver disease is due to intrinsic or idiosyncratic hepatotoxins. Liver parenchyma is then infiltrated by immunocompetent cells. Eosinophils are primarily tissue leukocytes which are attracted into tissues by various chemoattractants, including chemokines. The aim of this study was to study eosinophils in the livers of patients with drug-induced liver disease., Methods: Immunohistochemical studies with antibodies against eosinophil cationic proteins (major basic protein, eosinophil-derived neurotoxin and eosinophil cationic protein), cytokines (interleukin 5 (IL-5), interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF)) and chemokines (eotaxin and RANTES (Regulated upon Activation Normal T cell Expressed and Secreted)) were performed to assess the in situ activation of the liver-infiltrating eosinophils of 14 patients with drug-induced liver disease and 19 controls., Results: Eosinophils were only observed in patients with drug-induced liver disease. Eosinophils were morphologically normal when hepatitis was due to paracetamol whereas eosinophils had granular changes when hepatitis was due to an idiosyncratic hepatotoxin. Eotaxin was detected in all patients with drug-induced liver disease, whereas RANTES was detected in three of them. IL-5, IL-3 or GM-CSF were not detected., Conclusions: In patients with drug-induced liver disease, the recruitment of eosinophils in the liver may depend on eotaxin expression. Eosinophil changes may vary according to the type of drug.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.