Extracorporeal organ support for critically ill patients: Overcoming the past, achieving the maximum at present, and redefining the future.

Extracorporeal organ support (ECOS) has made remarkable progress over the last few years. Renal replacement therapy, introduced a few decades ago, was the first available application of ECOS. The subsequent evolution of ECOS enabled the enhanced support to many other organs, including the heart [veno-arterial extracorporeal membrane oxygenation (ECMO), slow continuous ultrafiltration], the lungs (veno-venous ECMO, extracorporeal carbon dioxide removal), and the liver (blood purification techniques for the detoxification of liver toxins). Moreover, additional indications of these methods, including the suppression of excessive inflammatory response occurring in severe disorders such as sepsis, coronavirus disease 2019, pancreatitis, and trauma (blood purification techniques for the removal of exotoxins, endotoxins, or cytokines), have arisen. Multiple organ support therapy is crucial since a vast majority of critically ill patients present not with a single but with multiple organ failure (MOF), whereas, traditional therapeutic approaches (mechanical ventilation for acute respiratory failure, antibiotics for sepsis, and inotropes for cardiac dysfunction) have reached the maximum efficacy and cannot be improved further. However, several issues remain to be clarified, such as the complexity and cost of ECOS systems, standardization of indications, therapeutic protocols and initiation time, choice of the patients who will benefit most from these interventions, while evidence from randomized controlled trials supporting their use is still limited. Nevertheless, these methods are currently a part of routine clinical practice in intensive care units. This editorial presents the past, present, and future considerations, as well as perspectives regarding these therapies. Our better understanding of these methods, the pathophysiology of MOF, the crosstalk between native organs resulting in MOF, and the crosstalk between native organs and artificial organ support systems when applied sequentially or simultaneously, will lead to the multiplication of their effects and the minimization of complications arising from their use.

Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions.

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.

Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

Quality metrics in the management of acute stroke in Greece during the first 5 years of Registry of Stroke Care Quality (RES-Q) implementation.

Introduction: Establishment of a prospective stroke registry may promote the documentation and improvement of acute stroke care. We present the status of stroke management in Greece using the Registry of Stroke Care Quality (RES-Q) dataset. Methods: Consecutive patients with acute stroke were prospectively registered in RES-Q registry by contributing sites in Greece during the years 2017-2021. Demographic and baseline characteristics, acute management, and clinical outcomes at discharge were recorded. Stroke quality metrics, with a specific interest in the association between acute reperfusion therapies and functional recovery in ischemic stroke patients are presented. Results: A total of 3590 acute stroke patients were treated in 20 Greek sites (61% men, median age 64 years; median baseline NIHSS 4; 74% ischemic stroke). Acute reperfusion therapies were administered in almost 20% of acute ischemic stroke patients, with a door to needle and door to groin puncture times of 40 and 64 min, respectively. After adjustment for contributing sites, the rates of acute reperfusion therapies were higher during the time epoch 2020-2021 compared to 2017-2019 (adjusted OR 1.31; 95% CI 1.04-1.64; p < 0.022; Cochran-Mantel-Haenszel test). After propensity-score-matching, acute reperfusion therapies administration was independently associated with higher odds of reduced disability (one point reduction across all mRS scores) at hospital discharge (common OR 1.93; 95% CI 1.45-2.58; p < 0.001). Conclusions: Implementation and maintenance of a nationwide stroke registry in Greece may guide the stroke management planning, so that prompt patient transportation, acute reperfusion therapies, and stroke unit hospitalization become more widely accessible, improving the functional outcomes of stroke patients.

Impact of secondary sepsis on mortality in adult intensive care unit patients.

RATIONALE: Septic patients admitted to the intensive care unit (ICU) suffer from immune dysregulation, potentially leading to a secondary sepsis episode. This study aims to (i) assess the secondary sepsis rate, (ii) compare the second with the first episodes in terms of demographics, clinical and laboratory characteristics, and outcomes, and iii) evaluate the outcome of secondary sepsis. METHODS: A single-center, retrospective study (2014-2017) was conducted in a Greek ICU, including consecutive cases of adult patients admitted to the ICU for at least 48 h with a principal admission diagnosis of sepsis and stayed for at least 48 h. We searched for a secondary episode of sepsis following the primary-one. We performed survival analyses with Cox proportional hazard, Fine-Gray, and multistate models. RESULTS: In this study, 121 patients that fulfilled the eligibility criteria were included. The secondary sepsis group included 28 (23.1 %) patients, with episode onset, median (interquartile range), 9.5 (7.7-16.2) days after ICU admission, who had less frequently had a medical admission diagnosis, a microbiologically confirmed first episode, and the C-reactive protein was lower. The overall ICU mortality of the cohort was 44.6 %. The group that developed secondary sepsis had higher mortality, but significance was lost in Cox regression [Hazard ratio (95 % CI) 0.59(0.31-1.16)]. However, after multistate modeling adjustment, the attributable mortality was estimated at 43.9 % (95 %CI ± 14.8 %). CONCLUSION: Secondary sepsis was evident in a quarter of the study participants and may be associated with an increased risk of death.

Pregnancy and COVID-19.

Evidence indicates that SARS-CoV-2 infection increases the likelihood of adverse pregnancy outcomes. Modifications in the circulatory, pulmonary, hormonal, and immunological pathways induced by pregnancy render pregnant women as a high-risk group. A growing body of research shows that SARS-CoV-2 infection during pregnancy is connected to a number of maternal complications, including pneumonia and intensive care unit (ICU) hospitalization. Miscarriages, stillbirth, preterm labor, as well as pre-eclampsia and intrauterine growth restriction are also among the most often documented fetal implications, particularly among expecting women who have significant COVID-19 symptoms, often affecting the timing and route of delivery. Thus, prevention of infection and pharmacological treatment options should aim to minimize the aforementioned risks and ameliorate maternal, obstetric and fetal/neonatal outcomes.

ICU-Associated Gram-Negative Bloodstream Infection: Risk Factors Affecting the Outcome Following the Emergence of Colistin-Resistant Isolates in a Regional Greek Hospital.

Intensive care unit patients may present infections by difficult-to-treat-resistant Gram-negative microorganisms. Colistin resurfaced as a last resort antibiotic for the treatment of multi-drug-resistant Gram-negative bacteria. However, colistin might not improve survival, particularly after the emergence of colistin-resistant isolates. We aimed to (1) examine the first Gram-negative-associated-bloodstream infection (GN-BSI) effect on 28-day mortality and (2) distinguish mortality risk factors. From 1 January 2018 to 31 December 2019, we retrospectively studied all adult patients admitted for more than 48 h in the critical care department of a regional Greek hospital, with prevalent difficult-to-treat Gram-negative pathogens. We examined the patient records for the first GN-BSI. The local laboratory used broth microdilution to evaluate bacterial susceptibility to colistin. Seventy-eight patients fulfilled the entry criteria: adult and first GN-BSI. They developed GN-BSI on day 10 (6-18), while the overall mortality was 26.9%. Thirty-two and 46 individuals comprised the respective colistin-resistant and colistin-sensitive groups. The admission Acute Physiology Assessment and Chronic Health Evaluation II score was associated with acquiring colistin-resistant GN-BSI in the multivariable logistic regression analysis (οdds ratio (CI), 1.11 (1.03-1.21)). Regarding mortality, the index day sequential organ failure assessment score was solely associated with the outcome (hazard-ratio (CI), 1.23 (1.03-1.48), Cox proportional hazard analysis). GN-BSI was often caused by colistin-resistant bacteria. Concerning our data, sepsis severity was the independent predictor of mortality regardless of the colistin-resistance phenotype or empirical colistin treatment.

Gastroenterology and liver disease during COVID-19 and in anticipation of post-COVID-19 era: Current practice and future directions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global public health. The virus causes the clinical syndrome known as coronavirus disease 2019 (COVID-19), in which multiple organs can get affected. Apart from manifestations of the respiratory system, which predominate, its clinical presentation is frequently accompanied by symptoms of the gastro-intestinal (GI) tract and liver abnormalities. The correlation of symptoms and abnormalities with disease severity is discussed, leading to ambiguous results from international literature. Moreover, the disease infects patients with co-existing liver and GI disorders affecting both their health status and the availability of healthcare services provided to them. The risk of transmission of the disease during aerosol-generating procedures has changed the diagnostic approach and follow-up algorithms for liver and GI diseases. For the safety of both doctors and patients, telemedicine and distant evaluation have become everyday practice, whereas several routines and emergency visits at outpatient and emergency departments have been postponed or delayed. Vaccination against SARS-CoV-2 is underway, providing hope to humanity and the expectation that the post-COVID-19 era is near. This review aims to update knowledge about the manifestations of COVID-19 related to liver and GI diseases and the effect of the pandemic on the diagnostic and therapeutic procedures for these diseases with a special focus on how current practices have changed and what changes will possibly remain in the future.

Promyelocytic Leukemia Antigen Expression: a Histological Marker for Primary Biliary Cholangitis Diagnosis?

BACKGROUND AND OBJECTIVES: Distinguishing primary biliary cholangitis (PBC) from other cholestatic diseases at the histological level could be assisted by new methods, such as immunohistochemical staining of specific antigens. METHODS: We evaluated whether the detection of promyelocytic leukemia protein (PML) can serve as a specific and sensitive marker for PBC diagnosis. Liver biopsies from 26 PBC patients, 20 primary sclerosing cholangitis (PSC), 37 viral hepatitis, 11 non-alcoholic steatohepatitis (NASH) and 5 normal patients were investigated after immunostaining with the anti-PML monoclonal PG-M3, IgG1 antibody. RESULTS: Immunoreactivity in bile ducts was expressed by the PML-score (quotient of positive ducts to the total number of portal tracts multiplied by 2). PML-score was higher in PBC as compared to controls (P < 0.001). Using a cutoff of 0.18, PML-score proved highly sensitive (84.6%) and specific (89.7%) for confirming PBC as compared to only 5% of PSC, 9.1% of NASH and 13.5% of viral hepatitis patients (P < 0.001). Irrespective of the underlying disease, patients with PML-score > 0.18 were older (P = 0.007), more often females (P < 0.001) with higher ALP (P < 0.001), γ-GT (P = 0.001) and IgM (P < 0.001) compared to the patients with PML-score < 0.18. CONCLUSIONS: We postulate that a simple PML immunohistochemical test could be sufficient for histopathological discrimination of PBC in problematic cases of undefined cholestatic disorders, including small-duct PSC and AMA-negative PBC cases.

Newly Diagnosed Acute Myeloid Leukemia in a Patient With Severe SARS-CoV-2 Infection.

We present a 68-year-old male patient with persistent and complicated SARS-CoV-2 infection who was diagnosed with acute myeloid leukemia (AML). The patient suffered from fever, cough and progressive dyspnea for 10 days and he was admitted to the intensive care unit due to respiratory failure and cytokine release syndrome (CRS). Despite a transient improvement of CRS by the implementation of supportive care, including also the administration of recombinant tissue plasminogen activator (rt-PA) and tocilizumab, his clinical course worsened over time. Thus, a bone marrow aspiration was performed revealing the presence of myeloblasts in a proportion of 32% and flow cytometry confirmed the diagnosis of AML-M1 according to FAB classification. Re-evaluation of peripheral blood tests revealed that the patient was admitted with anemia and thrombocytopenia that were never recovered during hospitalization. Due to the patient's poor clinical condition, no chemotherapy was applied, and he died of sepsis and multi-organ failure two days later. This case suggests that in all patients with a persistent and/or complicated infection, even during pandemics, the presence of an underlying hematologic malignancy should always be taken into consideration.

Combination of thrombolytic and immunosuppressive therapy for coronavirus disease 2019: A case report.

In a proportion of patients, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multisystem syndrome characterized by hyperinflammation, acute respiratory distress syndrome (ARDS), and hypercoagulability. A 68-year-old man with coronavirus disease 2019 (COVID-19) was admitted to the intensive care unit with respiratory failure, cytokine release syndrome (CRS), and skin ischemia - microthrombosis. Specific coagulation and inflammatory markers (D-dimer, ferritin, and C-reactive protein), along with the clinical picture, triggered the trial of recombinant tissue plasminogen activator (rt-PA) and tocilizumab. This was followed by resolution of the skin ischemia and CRS, while respiratory parameters improved. No major complications associated with rt-PA or tocilizumab occurred. The combination of rt-PA with targeted anti-inflammatory treatment could be a new therapeutic option for patients with COVID-19, ARDS, hyperinflammation, and increased blood viscosity.

Inadvertent direct pulmonary artery catheterization complicating the effort for subclavian venous cannulation and central venous catheter placement: A case report and review of the literature.

Subclavian access is commonly used in the intensive care unit (ICU) for central venous catheterization. Many complications have been reported during the placement of central venous catheters including pneumothorax, hemothorax, hematoma, and bleeding. The direct, through the thoracic wall, catheterization of pulmonary artery is a very rare one with only three previous reports in the literature. We report a patient who was catheterized for subclavian venous catheter placement, but the imaging techniques (chest X-ray and computed tomography with reconstruction of the images) revealed the direct positioning of the catheter into the pulmonary trunk, fortunately without other adverse events for the patient. Our case report in accordance with recent review of the literature strongly emphasizes the benefits of performing ultrasound-guided interventions in ICU.

Adult congenital heart disease with pulmonary arterial hypertension: mechanisms and management.

Adult congenital heart disease (ACHD) encompasses a range of structural cardiac abnormalities present before birth attributable to abnormal foetal cardiac development. The pulmonary circulation of patients with ACHD and intracardiac or extracardiac defects is often exposed to increased blood flow and occasionally to systemic pressures. Depending on the location and magnitude of the defect as well as the time of surgical correction, the patient with ACHD is at risk of developing pulmonary arterial hypertension (PAH), which dramatically increases morbidity and mortality. It is encouraging that therapies applied in idiopathic PAH and significantly improve outcome are also effective in ACHD-related PAH (ACHD-PAH). This review summarizes the challenges encountered in the diagnosis and management of ACHD-PAH.

Intravenous thrombolysis for acute ischemic stroke in Greece: the Safe Implementation of Thrombolysis in Stroke registry 15-year experience.

BACKGROUND: Intravenous thrombolysis (IVT) remains the only approved systemic reperfusion treatment for acute ischemic stroke (AIS), however there are scarce data regarding outcomes and complications of IVT in Greece. We evaluated safety and efficacy outcomes of IVT for AIS in Greece using the Safe Implementation of Thrombolysis in Stroke: International Stroke Thrombolysis Register (SITS-ISTR) dataset. METHODS: All AIS patients treated with IVT in Greece between December 2002 and July 2017 and recorded in the SITS-ISTR were evaluated. Demographics, risk factors, baseline stroke severity [defined using National Institutes of Health Stroke Scale (NIHSS)], and onset-to-treatment time (OTT) were recorded. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 3-month mortality rates. The efficacy outcomes evaluated a reduction in baseline NIHSS score at 2 and 24 h following IVT onset, 3-month favorable functional outcome [FFO; modified Rankin scale (mRS) scores of 0-1] and 3-month functional independence (FI; mRS-scores of 0-2). The safety and efficacy outcomes were assessed comparatively with previously published data from SITS national and international registries. RESULTS: A total of 523 AIS patients were treated with IVT in 12 Greek centers participating in the SITS-ISTR during the study period (mean age 62.4 ± 12.7; 34.6% women; median baseline NIHSS score: 11 points; median OTT: 150 min). The rates of sICH were 1.4%, 2.3%, and 3.8% according to the SIST-MOST, ECASS II, and NINDS criteria respectively. The median reduction in NIHSS score at 2 and 24 h was 3 [interquartile range (IQR): 1-5] and 5 (IQR: 2-8) points respectively. The 3-month FI, FFO and mortality were 66.5%, 55.6% and 7.9%. All safety and efficacy outcomes were comparable with available data from SITS-ISTR in other European countries. CONCLUSIONS: Our study underscores the safety and efficacy of IVT for AIS in Greece. Additional action is necessary in order to increase the availability of IVT in the Greek population and to include more centers in the SITS-ISTR.

Predictors of Need for Critical Care Support, Adverse Events, and Outcome after Stroke Thrombolysis.

BACKGROUND: Results from trials and international registries exhibit heterogeneity regarding safety, efficacy, markers of prognosis, and markers of the need for critical care support after intravenous thrombolysis (IVT) for strokes. The purpose of our study was to indentify such markers after performance of comparisons among patients who received thrombolysis in our intensive care unit. MATERIALS AND METHODS: Our study included 124 patients who received IVT in accordance with international criteria. Outcome measures of univariate and regression analyses resulted from comparisons between groups of patients with or without the need for critical care support (advanced life support and neurocritical care interventions), groups of patients developing or not developing primary adverse events (symptomatic intracranial hemorrhage [SICH] and/or Death and/or Serious systemic bleeding and/or New stroke) and groups of patients with different main outcome variables (mortality, functional independence at 3 months). RESULTS: Our results suggested that higher severity scores (Simplified Acute Physiology Score II, National Institutes of Health Stroke Scale) correlated with the need for critical care support, primary adverse events, and main outcome variables, whereas older age was significantly associated with fewer adverse events. Hyperlipidemia, symptom-to-needle time, and vascular disease were associated with functional capacity at 3 months, whereas diabetes mellitus and vascular disease correlated with the need for critical care support. CONCLUSION: Patients' age, hyperlipidemia, presence of vascular disease, Simplified Acute Physiology Score II (a novel marker), and National Institutes of Health Stroke Scale at 2 hours and at 7 days are independent predictors of the need for critical care support, adverse events, and clinical outcomes after thrombolysis.

Clinical significance of the fluctuation of primary biliary cirrhosis-related autoantibodies during the course of the disease.

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease characterized by the presence of antimitochondrial antibodies (AMA). PBC-specific antinuclear antibodies (ANA) have been characterized and associated with disease progression and outcome. We evaluated the clinical significance of the presence and serial changes in titers of AMA, PBC-specific ANA (anti-gp210, anti-sp100) and anti-chromatin antibodies. Over a median (IQR) period of 35 (36) months, 512 specimens were collected from 110 patients. Autoantibodies were detected by commercial ELISAs (INOVA Diagnostics). Biochemical, clinical, and histological status were included at initial presentation and during follow-up visits. The Mayo risk score was calculated as a prognostic index at each time point. Liver biopsy findings were classified according to Ludwig's classification and biochemical response to ursodeoxycholic acid was evaluated according to Pares. At baseline, AMA IgG and IgA, anti-gp210 IgG, anti-sp100 IgG and anti-chromatin IgG were detected in 92/110 (83.6%), 57/110 (51.8%), 5/110 (4.5%), 14/110 (12.7%), and 0/110 (0%) patients, respectively. Positivity for all autoantibodies apart from anti-chromatin, at baseline visit (n = 110 patients), in all tested sera (n = 512) as well as increased autoantibodies titers during follow-up were associated with biochemically and/or histologically advanced disease. A decrease of anti-sp100 titers but not of anti-gp210 titers during follow-up was associated with improvement of Mayo risk score (p = 0.025) and response to ursodeoxycholic acid (p = 0.016). These results suggest that detection of AMA and PBC-specific ANA was correlated with disease severity. Serial changes of anti-sp100 titers and not of anti-gp210 titers might prove useful for monitoring the disease course and treatment outcome.

Reactivation of resolved hepatitis B virus infection after immunosuppression: is it time to adopt pre-emptive therapy?

New therapeutic options like monoclonal antibodies (anti-CD20/rituximab) and hematopoietic stem cell transplantation (HSCT) have increased both the effectiveness of therapies and the risk for reactivation of Hepatitis B virus (HBV). We describe two cases with serological evidence of resolved HBV infection (hepatitis B surface antigen (HBsAg) negative/antibody to hepatitis B core antigen (anti-HBc) and antibody to hepatitis B surface antigen (anti-HBs) positive), who developed reverse seroconversion (clearance of HBsAb/appearance of HBsAg) with active HBV infection after treatment with combination of conventional chemotherapy, rituximab and autologous HSCT for hematological malignancies. Review of the literature highlights the increasing incidence of HBV reactivation in patients with resolved infection and raises concerns as to whether current guidelines for pre-chemotherapy screening with sensitive HBV-DNA assays and serial monitoring for anti-HBs titres should be implemented also for patients with resolved infection. Future studies should aim at clarifying the cost-benefit from administration of nucleoside analogues in these patients.

Salmonella enteritidis Infection Complicated by Acute Myocarditis: A Case Report and Review of the Literature.

Salmonella spp. is the cause of commonly encountered infections, with seasonal pattern of occurrence and worldwide distribution. Some of the clinical manifestations such as gastroenteritis and bacteremia are common, whereas others like mycotic aneurysms and osteomyelitis are infrequent especially in immunocompetent patients. Salmonella has been rarely described as a cause of myocarditis in the literature. We describe a case of an 18-year-old previously healthy male patient with myocarditis after Salmonella enteritidis infection. Clinical manifestations and diagnostic approach of this severe complication are discussed with a review of the literature.

Comparison of simplified score with the revised original score for the diagnosis of autoimmune hepatitis: a new or a complementary diagnostic score?

BACKGROUND AND AIMS: The International Autoimmune Hepatitis Group developed a simplified score for autoimmune hepatitis. We assessed this "new scoring system" and compared it with the International Autoimmune Hepatitis Group original revised score. METHODS: 502 patients were evaluated namely, 428 had liver diseases of various etiology [hepatitis B (n=109), hepatitis C (n=100), hepatitis D (n=4), alcoholic liver disease (n=28), non-alcoholic fatty liver disease (n=55), autoimmune cholestatic diseases (n=77), liver disorders of undefined origin (n=32) and miscellaneous hepatic disorders (n=23)], 13 had autoimmune hepatitis/overlap syndromes, 18 had autoimmune hepatitis/concurrent with other liver diseases and 43 had autoimmune hepatitis. RESULTS: The specificity of the simplified score was similar to that of the revised score (97% vs. 97.9%). The sensitivity in unmasking autoimmune hepatitis in autoimmune hepatitis/overlap syndromes was also similar in both systems (53.8% and 61.5%). However, the sensitivity for autoimmune hepatitis diagnosis in autoimmune hepatitis patients with concurrent liver disorders was lower by the new score (p=0.001). Liver biopsy proved to be the only independent factor for unmasking autoimmune hepatitis component among patients (p=0.003). CONCLUSION: The simplified score is a reliable and simple tool for excluding autoimmune hepatitis. However, both systems cannot unmask autoimmune hepatitis component efficiently in autoimmune hepatitis patients with concurrent autoimmune or non-autoimmune liver diseases. This study also strongly reiterates the importance of liver biopsy in the work-up of patients.

IgA anti-b2GPI antibodies in patients with autoimmune liver diseases.

INTRODUCTION: Recently, we reported a high prevalence of immunoglobulin G and/or immunoglobulin M anticardiolipin antibodies (aCL) in patients with autoimmune liver diseases, namely, autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC), which were independent of the respective isotypes of antibodies against beta2-glycoprotein I (anti-b2GPI). Immunoglobulin A (IgA) aCL and IgA anti-b2GPI are the least studied of the three specific isotypes either in antiphospholipid syndrome (APS) or in other conditions. METHODS: Therefore, we investigated the prevalence and clinical significance of IgA anti-b2GPI and IgA aCL by enzyme-linked immunosorbent assays in another set of Caucasian patients with autoimmune liver diseases (59 AIH, 96 PBC, and 37 PSC). The disease controls group consisted of 50 hepatitis C virus (HCV) patients, 50 hepatitis B virus (HBV), 30 alcoholic liver disease (ALD), 30 non-alcoholic steatohepatitis (NASH), and 110 healthy controls. RESULTS AND DISCUSSION: IgA anti-b2GPI prevalence was higher in AIH (50.8%) compared to PBC (p = 0.005), PSC (p = 0.008), NASH (p = 0.004), ALD (p = 0.01), and HCV (p = 0.002). The titers were also significantly higher in AIH compared to any other group of the study. IgA aCL prevalence was higher in AIH (33.9%) compared to PBC (p = 0.005), PSC (p = 0.014), NASH (p = 0.001), ALD (p = 0.004), and HCV (p < 0.001). IgA anti-b2GPI or IgA aCL were not associated with APS features in patients with liver autoimmunity. Of note, IgA anti-b2GPI and IgA aCL were associated with clinical and biochemical markers of disease severity in AIH and PBC. We demonstrated a high prevalence and high titers of IgA anti-b2GPI in patients with AIH compared to any other liver disease of the study. CONCLUSION: IgA anti-b2GPI and IgA aCL were associated with the severity and biochemical activity of AIH and PBC, but long-term prospective studies are needed to address whether this new finding is of clinical importance in AIH and PBC patients.