Multiple Autoimmune Propensity and B-Non-Hodgkin Lymphoma: Cause or Effect?

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

Ocular disorders as the prevailing manifestations of antiphospholipid syndrome: a case series

Introduction: Antiphospholipid syndrome is an autoimmune disorder characterized by either a history of vascular thrombosis (one or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ) or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The systemic features of the syndrome are characterized by large variability depending on the affected organ(s). Among them, neurological and behavioural disturbances, dermatological features as livedo reticularis and renal, ocular, liver or valvular heart manifestations have been reported in antiphospholipid syndrome patients. However, studies on the frequency and clinical presentation of the ocular manifestations as the prevailing (first) sign of antiphospholipid syndrome in patients suffering from "unexplained" ocular disease are missing. Herein, we present three cases suffering from unexplained ocular disease as first manifestation of antiphospholipid syndrome. Case presentation: All the three patients were referred to our department because of unexplained ocular features from the anterior or posterior segment and unexplained neuroophthalmologic symptoms. The first patient had bilateral retinal occlusive disease, the second and the third patient had unilateral nonarteritic anterior ischemic optic neuropathy with macular oedema. Moderate to high levels of antiphospholipid antibodies were detected in all of them at baseline as well as 6 to 12 weeks after initial testing confirming the presence of antiphospholipid antibodies. Anticoagulant treatment with acenocoumarol was instituted resulting in stabilization and/or improvement of ocular signs in all of them. Conclusion: Due to the important diagnostic and therapeutic implications of antiphospholipid syndrome, the possibility of ocular features as the first clinical manifestation of antiphospholipid syndrome should be kept in mind of the physicians particularly in patients with no evident risk factors for ocular disease. In this case, prompt anticoagulant treatment and close follow-up seem to be essential for vision salvation and stabilization. © 2009 Tsironi et al; licensee BioMed Central Ltd

The revised international autoimmune hepatitis score in chronic liver diseases including autoimmune hepatitis/overlap syndromes and autoimmune hepatitis with concurrent other liver disorders

Background. We conducted a study in order to determine the usefulness and diagnostic value of International Autoimmune Hepatitis Group (IAHG) score in non-autoimmune hepatitis (AIH) hepatic disorders as well as in AIH/overlap syndromes and in cases with coexistence of AIH and other liver diseases. Methods. We applied the IAHG score in 423 patients with liver diseases excluding patients with AIH, AIH/overlap syndromes and AIH with concurrent other liver disease namely, patients with chronic hepatitis B (n = 109), chronic hepatitis C (n = 95), chronic hepatitis D (n = 4), alchoholic liver disease (n = 28), non-alcoholic fatty liver disease (n = 55), autoimmune cholestatic liver diseases (n = 77), liver disorders of undefined origin (n = 32) and with miscellaneous hepatic disorders (n = 23). 24 patients with AIH associated with any kind of liver disorder including 10 patients with AIH/overlap syndromes and 14 AIH with concurrent other liver disease were also investigated. 43 patients with AIH consisted the control group. Results. The specificity of the score was 98.1% while the sensitivity in unmasking AIH in patients with either AIH/overlap syndromes or AIH with concurrent other liver diseases was only 50% and 78.6%. In the binary logistic regression model, the presence of other autoimmune diseases (p < 0.001), the total histological score (p < 0.001) and positivity for autoantibodies (p < 0.05) were identified as independent predictors for the presnce of AIH/ovea syndromes o AI with concurren other liver diseass. Conclusion. The IAHG scoring system has very good specificity for excluding AIH in patients with chronic liver diseases but not that sensitivity in order to unmask AIH/overlap syndromes or AIH with concurrent other liver diseases. The presence of other autoimmune diseases or autoantibody markers in the absence of hepatitis viral markers should alarm physicians for the possible presence of AIH either as "pure" AIH or in association with other liver disorders (AIH/overlap syndromes or AIH with concurrent other liver diseases). Under these conditions, liver histology seems essential and it must always be included in the work up of hepatic patients. © 2007 Papamichalis et al; licensee BioMed Central Ltd

Serologic indices of hepatitis B virus infection in military recruits in Greece (2004–2005)

BACKGROUND: The prevalence of hepatitis B virus infection in Greece has been decreasing over the last decades. However, recent epidemiological data are lacking. METHODS: We studied 1,840 Army recruits from 05/2004 until 10/2005, and performed serological testing for HBsAg, anti-HBsAg, and anti-HBcAg. We also examined their association with several factors, including age, residential area, socioeconomic class, and educational level. RESULTS: Mean age (± SD) of the recruits was 20.5 (± 2.1) years. Antibodies to HBV core antigen [anti-HBcAg (+)] were found in 31 (1.68%) of 1,840 participants. Only 6 (0.32%) were HBsAg (+)/anti-HBsAg (-)/anti-HBcAg (+), while 21 (1.14%) were HBsAg (-)/anti-HBsAg (+)/anti-HBcAg (+), and 4 (0.22%) were HBsAg (-)/anti-HBsAg (-)/anti-HBcAg (+). Overall, 1,144 recruits (62.17%) had antibodies against HBsAg [HBsAg (-)/anti-HBsAg (+)/anti-HBcAg (-)]; 665 recruits (36.14%) had undetectable anti-HBsAg levels. Multivariable analysis showed that younger age (OR: 0.87; 95% CI: 0.82–0.92) and advanced educational level (OR: 1.59; 95% CI: 1.32–1.93) were independently associated with serologic evidence suggestive of previous HBV vaccination. CONCLUSION: We document a further decline of the prevalence of chronic HBV infection among Greek military recruits, a fact that may support the effectiveness of the ongoing immunization programme

Autoimmune hemolytic anemia occurred prior to evident nephropathy in a patient with chronic hepatitis C virus infection: case report

BACKGROUND: Renal involvement in patients with chronic hepatitis C virus infection has been suggested to be due to a variety of immunological processes. However, the precise mechanism by which the kidneys are damaged in these patients is still unclear. CASE PRESENTATION: A 66 year old man presented with the sudden onset of autoimmune hemolytic anemia. Concomitant with a worsening of hemolysis, his initially mild proteinuria and hemoglobinuria progressed. On admission, laboratory tests revealed that he was positive for hepatitis C virus in his blood, though his liver function tests were all normal. The patient displayed cryoglobulinemia and hypocomplementemia with cold activation, and exhibited a biological false positive of syphilic test. Renal biopsy specimens showed signs of immune complex type nephropathy with hemosiderin deposition in the tubular epithelial cells. CONCLUSIONS: The renal histological findings in this case are consistent with the deposition of immune complexes and hemolytic products, which might have occurred as a result of the patient's underlying autoimmune imbalance, autoimmune hemolytic anemia, and chronic hepatitis C virus infection

Adherence to the screening program for HBV infection in pregnant women delivering in Greece

BACKGROUND: Hepatitis B infection (HBV) is a major Public Health Problem. Perinatal transmission can be prevented with the identification of HBsAg(+) women and administration of immunoprophylaxis to their newborns. A national prevention programme for HBV with universal screening of pregnant women and vaccination of infants is in effect since 1998 in Greece. METHODS: To evaluate adherence to the national guidelines, all women delivering in Greece between 17–30/03/03 were included in the study. Trained health professionals completed a questionnaire on demographic data, prenatal or perinatal screening for HBsAg and the implementation of appropriate immunoprophylaxis. RESULTS: During the study period 3,760 women delivered. Prenatal screening for HBsAg was documented in 91.3%. Greek women were more likely to have had prenatal testing. HBsAg prevalence was 2.89% (95%CI 2.3–3.4%). Higher prevalence of HBV-infection was noted in immigrant women, especially those born in Albania (9.8%). Other risk factors associated with maternal HBsAg (+) included young maternal age and absence of prenatal testing. No prenatal or perinatal HBsAg testing was performed in 3.2% women. Delivering in public hospital and illiteracy were identifiable risk factors for never being tested. All newborns of identified HBsAg (+) mothers received appropriate immunoprophylaxis. CONCLUSION: The prevalence of HBsAg in Greek pregnant women is low and comparable to other European countries. However, immigrant women composing almost 20% of our childbearing population, have significant higher prevalence rates. There are still women who never get tested. Universal vaccination against HBV at birth and reinforcement of perinatal testing of all women not prenatally tested should be discussed with Public Health Authorities

Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

\ua9 2022 The Authors. Background &amp; Aims: Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment. Methods: A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis. Results: The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term ‘complete biochemical response’ defined as ‘normalization of serum transaminases and IgG below the upper limit of normal’ be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as ‘&lt;50% decrease of serum transaminases within 4 weeks after initiation of treatment’. Remission is defined as liver histology with a Hepatitis Activity Index &lt;4/18. Intolerance to treatment was agreed to stand for ‘any adverse event possibly related to treatment leading to potential drug discontinuation’. Conclusions: These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints. Lay summary: Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents a statement on 5 agreed response criteria and endpoints: complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment, which can be used to guide future reporting

Unusual cardiovascular complications of brucellosis presenting in two men: two case reports and a review of the literature

Introduction: Brucellosis is a zoonosis with worldwide distribution, which is particularly endemic in many countries of the Mediterranean basin. Cardiovascular complications of this disease, such as endocarditis, myocarditis and pericarditis, are very rare, with even fewer cases of myocarditis or asymptomatic pericardial effusion in the absence of concomitant endocarditis being reported. Case presentation: We report two cases of brucellosis in two Caucasian men, aged 17 and 34 years old, with myocarditis and asymptomatic pericardial effusion, respectively. Of note, neither patient had concomitant endocarditis. The disease was confirmed serologically and by blood cultures. Both patients recovered completely after receiving appropriate antibiotic treatment without any sign of relapse during a follow-up of 12 months. Conclusion: These two cases emphasize that in endemic areas Brucella can be considered as a potentially causative agent of idiopathic pericardial effusion or myocarditis, even in the absence of concomitant endocarditis. This possibility could be taken into account particularly in cases where contraction of brucellosis is possible, such as occupational exposure or consumption of unpasteurized dairy products. © 2011 Gatselis et al; licensee BioMed Central Ltd

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study

Background and Aims: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). Approach and Results: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) &lt; 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) (p &lt; 0.0001). ALP normalization occurred in 5.4% (p=0.08) and 27.3% (p &lt; 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: −3.14 (p=0.02); placebo: −1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% (p=0.0008); 10 mg: 16.7% (p=0.03); placebo: 4%]. There were no serious treatment-related adverse events. Conclusions: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated