Diagnostic value of screening methods for the determination of antinuclear antibodies using indirect immunofluorescence on HEp-2 cells and enzyme immunoassay in autoimmune liver diseases.

Antinuclear antibodies (ANA) are a heterogeneous group of autoantibodies that react with various components of the cell nucleus and cytoplasm. ANA is the main serological marker for autoimmune liver disease (AILD). The aim of the study was to compare the diagnostic value of two methods of screening for the determination of ANA (indirect immunofluorescence reaction on HEp-2 cells (IIF -HEp-2) and enzyme-linked immunosorbent assay (ELISA) in the sera of AILD patients. The sera of 118 patients with AILD (51 with autoimmune hepatitis - AIH, 19 with primary biliary cholangitis - PBC, 48 with overlapping syndrome - OVERLAP), 30 patients with non-alcoholic fatty liver disease (NAFLD) and 30 healthy donors (HD) were studied. Determination of ANA by the IIF-HEp-2 method was carried out by visual assessment of samples under an AXIOSKOP 40 microscope, by ELISA - on an Alegria automatic analyzer. A weak degree of agreement between the positive and negative results of the ANA screening study using IIF-HEp-2 and ELISA (Cohen's kappa coefficient æ=0.4) was noted. Screening determination of ANA in patients with AILD by the IIF-HEp-2 method was distinguished by greater diagnostic sensitivity (DS) (68.6%) and a lower frequency of false negative results (31.4%) compared with ELISA (35.6% and 64.4 % respectively, p<0.05). The overall diagnostic specificity (DS) of the ANA study in IIF-HEp-2 was lower than with ELISA (66.7% and 86.7%, respectively, p<0.05). Both screening methods for determining ANA (IIF-HEp-2 and ELISA) were useful for diagnosing AILD (positive likelihood ratio - LR+: 2.1 and 2.6, respectively). In terms of the negative likelihood ratio (LR-), screening for ANA by the IIF-HEp-2 method, in contrast to ELISA, served as a "useful" test to exclude the diagnosis of AILD (0.5 and 0.8, respectively). The determination of ANA using IIF-HEp-2 is the most sensitive and "useful" screening test for the diagnosis of AILD, and ELISA is classified as a less "useful" screening method due to low diagnostic sensitivity and a high false-negative rate.

Important problems in the diagnosis and treatment of primary sclerosing cholangitis (based on the Russian consensus on diagnosis and treatment autoimmune hepatitis. Moscow, 2018).

The article is published based on the results of the Russian Consensus on the diagnosis and treatment of primary sclerosing cholangitis (PSC), discussed at the 44th annual Scientific Session of the CNIIG "Personalized Medicine in the Era of Standards" (March 1, 2018). The aim of the review is to highlight the current issues of classification of diagnosis and treatment of patients with PSC, which causes the greatest interest of specialists. The urgency of the problem is determined by the multivariate nature of the clinical manifestations, by often asymptomatic flow, severe prognosis, complexity of diagnosis and insufficient study of PSC, the natural course of which in some cases can be considered as a function with many variables in terms of the nature and speed of progression with numerous possible clinical outcomes. In addition to progression to portal hypertension, cirrhosis and its complications, PSC can be accompanied by clinical manifestations of obstructive jaundice, bacterial cholangitis, cholangiocarcinoma and colorectal cancer. Magnetic resonance cholangiography is the main method of radial diagnostics of PSC, which allows to obtain an image of bile ducts in an un-invasive way. The use of liver biopsy is best justified when there is a suspicion of small-diameter PSC, autoimmune cross-syndrome PSC-AIG, IgG4-sclerosing cholangitis. Currently, a drug registered to treat primary sclerosing cholangitis which can significantly change the course and prognosis of the disease does not exist. There is no unified view on the effectiveness and usefulness of ursodeoxycholic acid and its dosage in PSC. Early diagnosis and determination of the phenotype of PSC is of clinical importance. It allows to determine the tactics of treatment, detection and prevention of complications.

Important problems in the diagnosis and treatment of autoimmune hepatitis (based on the Russian consensus 2017).

The analysis of publications devoted to the Russian Consensus on the Diagnostic and Treatment of Autoimmune Hepatitis (AIH), which was considered at the 43rd annual Scientific Session of the CNIIG From Traditions to Innovation (March 4, 2017) is carried out. The presence of clear algorithms and recommendations for the diagnosis and treatment of AIH significantly help the doctor in real clinical practice, but do not exclude a personified approach to the patient.

Hepatic decompensation associated with an interferon-free antiviral therapy in patients with HCV-cirrhosis.

Today, there is no complete clarity about the pathogenetic mechanisms of the hepatic decompensation in patients with HCV-cirrhosis during the course of direct-acting antiviral (DAAs) therapy. The current article describes several clinical observations of decompensation (with the development of liver failure and portal hypertension) in cirrhotic patients during the course of DAAs-therapy of hepatitis C. The authors present contemporary views and their own assumptions about the possible mechanisms of the hepatic decompensation associated with DAAs-therapy in patients with liver cirrhosis.

[Diabetes mellitus and nonalcoholic fatty liver disease: The verges of contingency]. / Sakharnyi diabet i nealkogol'naya zhirovaya bolezn' pecheni: grani sopryazhennosti.

AIM: To estimate the incidence of hepatic steatosis (HS) and liver fibrosis (LF) in patients with diabetes mellitus (DM), by applying the noninvasive techniques of liver fibroelastometry (LFE) and a battery of fibrotests (FTs); to determine their diagnostic value and to identify factors influencing the development of LF. SUBJECTS AND METHODS: A comprehensive examination was made in 82 diabetic patients (mean age, 56.7±12.7 years; p=0.033). The data were statistically evaluated using ROC curve analysis, correlation and single-factor analyses of variance, and multiple logistic regression analysis. RESULTS: FTs and LFE revealed that the DM patients had liver cirrhosis (LC) (METAVIR F4) in 12 (14.6%) and 15 (18.2%) patients, respectively. Those showed clinically significant fibrosis (METAVIR fibrosis stages F2-3) in 19 (23.1%) and 23 (28%) patients, respectively. Varying degrees of HS were present in 79 (96.3%) patients. LFE and FTs demonstrated comparable results in detecting LC (the area under the receiver operating characteristics curve (AUROC), 0.83 and 0.81, respectively). The development of LF is influenced by factors, such as the degree of HS, obesity, the activity of an inflammatory process, and the level of alanine aminotransferase and α2-macroglobulin. CONCLUSION: Diabetic patients are at high risk for NAFLD to develop LF and LC. LFE and FTs showed a comparably high accuracy in the diagnosis of LC in patients with DM and these may be used for screening. With allowance made for the existing risk factors of LF and LC, it is necessary to identify groups of patients with DM for further examination and follow-up. Patients who are diagnosed with stage F4 should be examined carefully to evaluate concurrent diseases and to make liver biopsy.

[A new non-invasive method for assessing steatosis in chronic liver diseases].

AIM: To assess the diagnostic accuracy of the controlled attenuation parameter (CAP) to determine the grade of hepatic steatosis (HS) in patients with chronic liver diseases (CLD) of different etiologies and to compare the obtained results with morphological findings. MATERIALS AND METHODS: A total of 45 patients (18 men and 27 women) aged 25 to 73 years with CLD were examined. All the patients underwent liver puncture biopsy for assessing the HS index and fibrosis stage, as well as determination of hepatic elasticity (F, kPa) for estimating the stage of fibrosis and the grade of HS by CAP (S, dB/m) using a FibroScan device. When assessing HS, the CAP values of <229, 230-249, 250-276, and more than 277 dB/m correspond to HS grade 0 (S0), S1, S2, and S3, respectively. This is a pilot study in Russia. RESULTS: CAP is a rather high effective method in determining the absence of steatosis (S0) (the area under the receiver operating characteristics curve (AUROC) was 0.78) and severe steatosis (S3) (AUROC 0.90). AUROC was 0.64 and 0.59 for HS S1 and S2, which is regarded as satisfactory and poor RESULTS: respectively. Only 3 out of the 45 patients had HS, as evidenced by morphological examination; and the results of CAP showed another result; all the other cases had a HS grade corresponding to S1. In the entire cohort of the examinees, the sensitivity, specificity, and accuracy of CAP was 86, 69.5, and 78%, respectively; AUROC was 0.77 (95% CI, 0.6587-0.9006; p=0.40). CONCLUSION: CAP is a promising method for the rapid and non-invasive diagnosis of HS in patients with CLD. At the same time, our findings show that it is necessary to clarify the quantitative indicators of the compliance of CAP and morphological evaluation of HS.