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We report a case of multiple autoimmunity consisting of the presence of autoimmune haemolytic anaemia (AIHA), antimitochondrial antibodies (AMAs), and antiphospholipid antibodies (APLAbs) as the presenting manifestations of an extrahepatic B-non-Hodgkin lymphoma (B-NHL) in a 63-year-old woman. The patient presented with fatigue attributed to severe AIHA. Due to increased serum IgM and 𝛾 -GT levels, an investigation for AMA was performed, which proved positive with anti-M2 specificity. A prolongation of activated partial thromboplastin time (aPTT) led to the determination of APLAbs (lupus anticoagulant and other APLAbs) which were also positive. Bone marrow biopsy in combination with immmunohistochemical studies established the diagnosis of lymphoplasmacytic B-NHL. Ten months later, B-NHL was in remission while AMA and APLAbs were still positive. In conclusion, we documented the coexistence of multiple autoimmune reactions together with B-NHL highlighting the possible common pathogenetic pathways of the two entities.

Background Development of organ- and non-organ-specific autoantibodies has been reported in hepatitis C virus patients treated with interferon-alpha plus/minus ribavirin. Aims To address whether prevalence and the titre of gastric parietal autoantibodies and non-organ-specific autoantibody in hepatitis C virus-treated patients were affected by therapy, and if the development of these antibodies carries any clinical significance on the response to treatment, as few studies in adults have been strictly designed to address the above hypothesis. Methods Samples at three time-points (baseline, end of treatment, end of followup) from 102 hepatitis C virus patients (39 sustained responders, 26 relapsers, 33 non-responders; four lost in follow-up) were studied for gastric parietal autoantibodies and/or non-organ-specific autoantibody by indirect immunofluorescence, commercial and in-house enzyme-linked immunosorbent assays. Results Sustained virological and biochemical response was associated with antinuclear antibody absence (end of treatment or end of follow-up), decrease of smooth-muscle antibody titres during therapy and gastric parietal autoantibodies negativity at baseline. However, after multivariate analysis only antinuclear antibody positivity at the end of treatment and increase of smooth-muscle antibody titres were associated with worst treatment response, independently of known factors of worst treatment outcome. Conclusions We were able to demonstrate a negative correlation between the efficacy of anti-viral treatment for hepatitis C virus and the presence of antinuclear antibody and smooth-muscle antibody before treatment, or their increase during therapy.

BACKGROUND: Open-heart procedure is characterized by a high-risk for contracting blood-borne infections. We evaluated the prevalence of several markers of hepatitis viruses (B-E) and human T-cell lymphotropic virus types I/II (HTLV-I/II) in a consecutive series of patients who had undergone open-heart surgery. METHODS: 204 patients and 158 selected age- and sex-matched healthy volunteers were investigated. Samples were collected at least 6-12 months postoperatively. Commercial enzyme immunoassays and confirmatory immunoblot assays for HCV, HEV and HTLV-I/II were used. RESULTS: None of the subjects tested positive for antibodies to HTLV-I/II. Prevalence of markers of past HBV infection and antibodies to HEV (anti-HEV) were higher in patients than in healthy controls (anti-HBc: 45.1% vs. 31%, p=0.009; anti-HBs: 31.9% vs. 22.2%, p=0.02; anti-HBe: 32.4% vs. 10.1%, p=0.000; anti-HEV: 5.4% vs. 0%, p=0.008). HBsAg and antibodies to HCV did not differ between the groups. CONCLUSIONS: HTLV, HBsAg and HCV infection markers did not differ between patients and healthy controls. However, patients had significantly increased prevalence of markers of previous HBV infection suggesting that an intensive vaccination schedule against HBV preoperatively might be helpful in minimizing the risk. The increased prevalence of anti-HEV in cardiac patients requires further investigation. Prospective studies are needed in order to definitely address whether the high prevalence of exposure to HBV and HEV infections in patients who had undergone open-heart surgery is procedure-related or not and whether it has any impact on morbidity of these patients. Eur J Intern Med

BACKGROUND: The risk of infection with transfusion-transmitted viruses has been reduced remarkably. However, a zero-risk blood supply remains a popular goal. Some authorities have introduced the screening for antibody to HBc (anti-HBc) as a surrogate test for the presence of several infectious agents. A 3-year prospective study was conducted in the Epirus region of Greece to determine the prevalence of several blood-borne viruses. One component of the study was the prevalence of HBV infection markers and the potential value of anti-HBc testing of donors in this area. STUDY DESIGN AND METHODS: Between January 1, 1995, and December 31, 1997, some 6696 donors were investigated for the presence of HBV infection markers by standard EIAS: Every sample that tested HBsAg-negative but anti-HBc-reactive alone or in combination with either or both antibodies to HBV e antigen (anti-HBe) and low-titered antibodies to HBsAg (anti-HBs

OBJECTIVE: Chronic infection with hepatitis C virus (HCV) has been found to be associated with various diseases known as extra-hepatic manifestations of HCV. Recently, HCV has been implicated as a cause of the antiphospholipid syndrome (APLS). We conducted a study in a well-characterized area for epidemiological and prospective studies in the north-western part of Greece in order to address whether an aetiopathogenesis exists between HCV and APLS. DESIGN: Seventy-five patients with chronic hepatitis C were investigated for the presence of anti-cardiolipin antibodies (anti-CL) and for a past medical history supportive to the diagnosis of APLS. In addition, 24 patients with well-defined APLS (primary or secondary) and 12 patients with systemic lupus erythematosus (SLE) were tested for the presence of markers of HCV infection (anti-HCV and HCV RNA). The SLE patients were anti-CL-positive but none of them had developed any of the known clinical features of APLS. In addition, 267 healthy subjects were investigated for the presence of anti-CL. METHODS: IgG and IgM anti-CL were determined by a quantitative isotype-specific solid phase enzyme-linked immunosorbent assay set up in our laboratory. Anti-HCV was determined using a third-generation enzyme immunoassay and a confirmatory third-generation recombinant immunoblot assay. Active virus replication was defined by the detection of HCV RNA using a combination assay based on a reverse transcriptase polymerase chain reaction and a DNA enzyme immunoassay. RESULTS: Of the HCV patients, 37.3% had IgG and/or IgM anti-CL (P

BACKGROUND/AIMS: The therapeutic experience of interferon-alpha therapy against hepatitis D virus infection in affected children is rather limited. For this reason, we conducted a retrospective study (duration: 1991-1995) in order to evaluate the efficacy and the safety of interferon-alpha in children suffering from chronic hepatitis D in Northwestern Greece. METHODOLOGY: Seven children who were found to be infected with HDV in a total of 324 children seropositive for hepatitis B virus infection during the 5-year period of the study were treated with interferon-alpha, 3 x 10(6) U/m2 body surface area, intramuscularly or subcutaneously, 3 times weekly for 1 year (after an informed consent obtained from their parents). Patients were assessed monthly by hematological serological and biochemical tests. Clinical progress, levels of serum alanine aminotransferase, hepatitis D ribonucleic acid (HDV-RNA) and hepatitis B deoxyribonucleic acid (HBV-DNA), seroconversion of hepatitis B surface antigen (HBsAg) and Hepatitis Be Antigen (HBeAg) and liver histology were used as response criteria. RESULTS: Posttreatment alanine transferase levels were significantly reduced (P < 0.05) but Immunoglobulin M and total anti-hepatitis D virus (anti-HDV) antibodies remained positive in all, while hepatitis D ribonucleic acid persisted positive in 4 cases. In addition, no seroconversion of HBsAg or HBeAg was noted and the liver histology progress was disappointing. Side effects including mild fever, arthralgias and malaise and reversible neutropenia and thrombocytopenia were common, but not particularly disturbing. Nevertheless, the children remained fully active on treatment, felt well and attended school. Initially 4 children had been below the 10th percentile for weight and height. All thrived during treatment and two crossed above the 10th percentile indicating height velocity and body mass index increase. CONCLUSIONS: The administration of regular interferon-alpha doses for treating children with chronic hepatitis D was safe as attested by the mild side effects and the objective clinical criteria regarding their growth, but relatively ineffective. Although the prevalence of hepatitis D virus infection is now generally decreased, this study indirectly indicates that more effective agents and new approaches at the molecular level of the hepatitis D virus genome are urgently warranted for its control in individuals already infected with the virus. Finally, the poor therapeutic results in the present study further enhance the necessity of the expanded vaccination against Hepatitis B virus according to the World Health Organization's recommendations. Hepatogastroenterology

Nephrol Dial Transplant

Hepatology

Ann Intern Med

BACKGROUND: Immunologic alterations have been reported in chronic haemodialysis (HD) patients. Some HD patients may have, therefore, an inability to produce detectable amounts of serum antibodies to hepatitis C virus (anti-HCV). Previous studies have shown the presence of HCV viraemia in anti-HCV-negative HD patients (ranging from 1 to 15%). However, the universal epidemiologic impact of these cases remains uncertain since there are conflicting results. In this context, we conducted a study in an attempt to investigate the presence of HCV viraemia among anti-HCV-negative HD patients in a well-defined geographic area of the northwestern part of Greece. METHODS: During a 6 month period, 81 anti-HCV-negative HD patients were tested twice for the presence of HCV RNA, using the reverse transcriptase polymerase chain reaction (RT-PCR) combined with a DNA enzyme immunoassay (DEIA). At the same time, periodic testing for anti-HCV by two commercially available third generation assays was done. In addition, 15 anti-HCV-positive HD patients and 20 non-HD patients with well established chronic HCV infection used as internal controls were tested for the presence of HCV RNA and anti-HCV. RESULTS: None of the anti-HCV-negative HD patients were shown to be viraemic by the combined RT-PCR and DEIA method. During the same time period, all remained anti-HCV negative by the third generation assays. By contrast, all the patients with known HCV-infection were positive by the two enzyme immunoassays, whereas 13 anti-HCV-positive HD patients (86.7%) and 18 non-HD patients (90%) were viraemic by RT-PCR. CONCLUSIONS: This study demonstrated that routine HCV RNA testing in anti-HCV-negative HD patients appears not to be necessary particularly when third generation assays are used for the detection of anti-HCV. Nephrol Dial Transplant

OBJECTIVE: Alpha-interferon therapy may occasionally account for immune-mediated phenomena. This study was conducted in an attempt to investigate the incidence of the development of immune-mediated dermatological diseases during alpha-interferon therapy in patients with chronic viral hepatitis. The latter has not been evaluated prospectively, whereas most of the previous studies examined small numbers of interferon treated patients or consisted of case reports. DESIGN: A prospective case-control study. SETTING: A tertiary referral centre. PARTICIPANTS: One hundred and twenty consecutive patients with chronic viral hepatitis (67 with hepatitis B, 45 with hepatitis C, six with both hepatitis viruses, and two with delta hepatitis) were evaluated during a course of alpha-interferon therapy. In addition, 120 consecutive patients with chronic liver diseases (disease control group), who had never received alpha-interferon therapy, were evaluated during the period of the study (at least for 12 months). INTERVENTIONS: Recombinant alpha-interferon at a dose of 4.5 or 5 million units subcutaneously (s.c.) three times per week for 6 to 12 months was administered to patients with hepatitis B. The patients with chronic hepatitis C were treated with 3 million units s.c. three times per week for 12 to 18 months. The patients with chronic hepatitis B and C infections received 4.5 million units for 6 months, and then 3 million units for an additional 6 to 12 months. Finally, the patients with chronic delta hepatitis received 5 million units for 1 year or more. MAIN OUTCOME MEASURES: To assess prospectively the incidence of these dermatological disorders during alpha-interferon therapy and to estimate if there is any relationship between their development and the clinical, laboratory or other characteristics of the patients with chronic hepatitis. RESULTS: Three to 6 months after the initiation of alpha-interferon three patients with chronic viral hepatitis (two with hepatitis C and one with hepatitis B) developed lichen planus, whereas one patient with hepatitis C developed relapsing aphthous stomatitis. The development of these disorders was significantly associated only with the presence of antinuclear antibodies before the initiation of alpha-interferon (P=0.000000). None of the patients from the disease control group had such a manifestation during the follow-up. Lichen planus resolved after the end of therapy in all of them. In contrast, therapy was discontinued in the patient who developed aphthous stomatitis, owing to the painful lesions. CONCLUSIONS: This study demonstrated that alpha-interferon may rarely (3.3%) induce immune-mediated dermatological disorders, especially lichen planus. The development of these disorders may reflect a subclinical or covert autoimmune background of patients, as suggested by the presence, although in low titres, of antinuclear antibodies. However, when lichen planus developed, it was mild, did not require the discontinuation of therapy and resolved after alpha-interferon administration had ceased. Eur J Gastroenterol Hepatol

Lancet

Intravenous heroin abusers comprise a high risk group for hepatitis B and C viruses (HBV and HCV) infection. Chronic alcoholics with liver disease (LD) also comprise a high risk group for HBV infection whereas the frequency of antibodies to HCV (anti-HCV) ranges from 27-42.6%. In this study, HBV and HCV infection markers were determined in alcoholic patients with (83 patients) or without LD (68 patients) in order to assess the prevalence of these markers (HBsAg, HBsAb, HBcAb and anti-HCV). The reason for the study was a lack of established data in this group of patients in Greece. The disease control groups consisted of 70 non-alcoholic hospitalized patients and 60 heroin addicts, whereas 1342 healthy blood donors were also investigated. Our results showed significantly increased prevalence of HBV infection markers in chronic alcoholic patients compared to healthy controls and non-alcoholic hospitalized patients. The findings were independent of the presence or absence of LD. In contrast to heroin addicts, where anti-HCV antibodies were observed in 90%, there was no difference in the prevalence of anti-HCV antibodies in chronic alcoholics (with or without LD), nonalcoholic hospitalized patients or healthy controls. In conclusion, we found that in this area of north-western Greece, chronic alcoholics, independent of the presence of LD, comprise a high risk group for HBV infection but very rarely have HCV infection. The latter finding may reflect technical or socio-economic differences regarding the lifestyle of our patients, and our population in general. Eur J Epidemiol

Immune system disturbances have been implicated in the pathogenesis of essential hypertension. The aim of this study was to determine the levels of the interleukin-1 beta and soluble interleukin-2 receptors in serum samples from 114 hypertensive patients before any drug therapy because there are no well-established data regarding these immunologic mediators in essential hypertension. We found increased levels of interleukin-1 beta in 59.6% of patients, while soluble interleukin-2 receptors were not detected. The interleukin-1 beta levels were significantly higher in patients than in healthy controls (P = 0.0001). We conclude that patients with essential hypertension have high levels of interleukin-1 beta but not indicators of cellular immune activation in their sera. Further studies are in progress in order to confirm, explain and assess the clinical utility of the above findings. Eur J Clin Invest

Serum interleukin-1 beta (IL-1 beta) and soluble interleukin-2 receptor (sIL-2R) levels were examined in patients with hyperthyroidism due to Graves' disease (GD) and toxic nodular goitre (TNG) before and during antithyroid drug therapy. A total of 32 patients were studied; 23 patients (14 with GD and nine with TNG) were in a hyperthyroid state (group A) and nine patients (four with GD and five with TNG) were in a euthyroid state, under carbimazole or methimazole treatment (group B). Ten hyperthyroid patients from group A (seven with GD and three with TNG) were also examined while euthyroid on treatment (Subgroup A). Serum was taken from all patients for the measurement of sIL-2R, IL-1 beta, total T4 (TT4), total T3 (TT3) and TSH concentrations. The results were compared with those from 30 normal controls. Serum sIL-2R levels were higher in Group A (671.3 +/- 74.0 U mL-1, mean +/- SE), than in Group B (214.1 +/- 61.8 U mL-1) and controls (149 +/- 14.8 U mL-1), P < 0.001. Similarly, the subgroup of 10 patients had higher levels of sIL-2R during the hyperthyroid phase than while euthyroid (P < 0.001). There was a positive correlation between sIL-2R values and levels of T4 and T3. In contrast, serum IL-1 beta levels were higher in Group B patients (197.5 +/- 39.2 pg mL-1) compared with those in Group A (66.5 +/- 17 pg mL-1, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Clin Invest

A patient with Crohn's disease (CD) subsequently developed the clinical and histological features of hidradenitis suppurative (HS). So far, only five cases with such an association have been reported. Azathioprine (150 mg/d) and methylprednisolone (16 mg/d) for CD combined with isotretinoin (0.7 mg/kg) and periodic administration of antibiotics for HS were used. The treatment was satisfactory, and the patient is now in clinical remission for both diseases. J Clin Gastroenterol

J Hepatol

BACKGROUND: Since 1991, thousands of refugees from southern Albania have entered north-western Greece, an area with low-to-moderate endemicity for infection with hepatitis viruses. We examined the prevalence of several markers of viral infection in this population in order to ascertain the likely impact of its presence on the epidemiology of hepatitis infections in north-western Greece. DESIGN: Consecutive unselected serum samples were obtained from refugees resident in three different reception camps. SETTING: A university hospital. STUDY POPULATION: One thousand and twenty-five refugees (662 males and 363 females, age range 0-81 years) and 1984 healthy controls (1293 males and 691 females, age range 0-80 years). INTERVENTIONS: None. RESULTS: We found a significantly greater prevalence of markers of infection with hepatitis A virus (prevalence of antibodies to hepatitis A virus 98.2%), hepatitis B virus (HBV; prevalence of HBV s antigen 22.2%, prevalence of HBV c antibody 70.6%, prevalence of HBV s antibody 40.5%, prevalence of HBV e antigen 21.1%, prevalence of HBV e antibody 46.2%), hepatitis C virus (prevalence of antibodies to hepatis C virus 1.75%) and hepatitis D virus (prevalence of antibodies to hepatis D virus 12.7%) among refugees from southern Albania than in healthy Greek controls. These markers were found with significantly greater frequency among younger refugees (< 30 years of age) than in older members of the same population. CONCLUSIONS: We conclude that refugees from southern Albania are a new immigrant population characterized by a high incidence of infection with hepatitis A, B and D viruses. This finding may reflect the low socioeconomic status of the immigrant population and the poor hygienic conditions experienced by its members. The high incidence of HBV and HDV infections in the population from Albania will probably increase the prevalence of infection with these viruses in Ioannina and subsequently in the whole of the Epirus region. We therefore believe that rigorous adherence to general precautions and the initiation of hepatitis B vaccination programmes will be necessary in future, both in our area and in Albania. Eur J Gastroenterol Hepatol

J Hepatol

To assess the degree of immune system activation associated with addiction or hepatotropic viruses infection, we examined 60 HIV-negative heroin addicts for the presence of hepatitis B virus (HBV) infection markers, hepatitis C virus antibodies (anti-HCV), various auto-antibodies, and serum levels of soluble interleukin-2 receptors (sIL-2R). In addition, 28 anti-HCV positive patients comprising the disease control group, were also examined. Our results demonstrated a high prevalence of anti-HCV antibodies (61.7% and 90% with 1st and 2nd generation ELISA, respectively). Eighty-seven percent (87%) of the addicts positive for anti-HCV by the latter and 92.8% of the disease control patients, were also positive with 2nd generation recombinant immunoblot assay (RIBA-II). In 88.9% of anti-HCV positive addicts, antibody to C22-3 was the predominant (anti-C33c in 81.5%). Antibodies to C33c and C22-3 polypeptides were also more frequent in disease control group (92.8% and 85.7%, respectively). Anti-HCV antibodies were associated with increased transaminases (ALT or AST, P < 0.05), as well as with longer duration of addiction (P < 0.005). HBV infection markers (HBsAg, anti-HBc only and anti-HBs) were also present in the addicts (5%, 28.3% and 26.7%, respectively). Rheumatoid factors (RF) were detected in 36.7%, antinuclear antibodies (ANA) in 11.7%, antibodies (IgG and/or IgM) against cardiolipin (anti-CL) and double stranded DNA (anti-ds DNA) in 20% and 50%, respectively. RF, ANA, anti-CL and anti-dsDNA antibodies were also detected in the disease control group (32.1%, 89.3%, 28.5% and 28.5% respectively).(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Clin Invest