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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

To assess the association of the CYBA, NOS3, and MTHFR gene polymorphisms and a rate of fibrosis progression in chronic hepatitis C (CHC).One hundred and nine CHC patients with the verified stage of liver fibrosis and cirrhosis at its onset were examined. The disease duration was determined in all the patients and additional risk factors of liver lesion were absent. A group of rapidly progressive fibrosis comprised 55 patients with a calculated fibrosis progression rate of 0.130 fibrosis units/year or higher and 54 patients with a progression rate of less than 0.130 fibrosis units/year were assigned to a slow fibrosis group. A compression group consisted of 299 healthy blood donors. The polymorphism of the genes under study was determined by polymerase chain reaction-restriction fragment length polymorphism analysis.The mutant TT genotype of the CYBA gene was significantly more common in the CHC patients with rapidly progressive fibrosis than in those with slowly progressive fibrosis (odds ratio for TT 9.09 at 95% confidence interval, 1.09 to 74.83; p = 0.0161). No significant differences were found in the distribution of the alleles and genotypes of the NOS3 and MTHFR genes between the groups of patients with slowly and rapidly progressive fibrosis.The findings make it possible to regard the TT genotype of the CYBA gene from the C242T locus as profibrogenic and as one of the markers of the poor course of CHC.

Chronic viral hepatitides B and C are systemic diseases with a great number of extrahepatic manifestations caused by different immune abnormalities due to viral replication in and outside the liver and to the direct pathological effects of viral particles. Many of them can be the only manifestation of the infection and come to the foreground in its clinical picture, by determining the prognosis of the disease.

To study the incidence and prognostic significance of extrahepatic manifestations of chronic HCV-infection with low activity of hepatic process and to specify treatment policy.Sixty-two patients with low-active chronic hepatitis C (CHC) entered the study. Blood samples from all the patients were studied clinically, biochemically, immunologically and virusologically. In 58 patients the diagnosis was confirmed morphologically (liver tissue).Systemic manifestations of CHC were observed in 23 (37.1%) patients, in 12 of them they were associated with cryoglobulinemia. Most frequent was cryoglobulinemic vasculitis with skin (12.9%) and joint (9.7%) involvement, cryoglobulinemic glomerulonephritis (11.3%), arthralgia without association with cryoglobulinemia (11.3%). Independent risk factors for development of systemic disorders in CHC of low activity comprised female gender, age over 45, the disease duration and presence of cryoglobulinemia.CHC of low activity is characterized by high occurrence of systemic manifestations primarily associated with cryoglobulinemia. Renal affection with development of cryoglobulinemic glomerulonephritis is most prognostically significant.

To examine clinical features of Sjogren's syndrome (SS) and morphological picture of the lesser salivary glands (LSG) in chronic hepatitis C (CHC).The examination of 42 patients with SS and chronic HCV infection (mean age 44.3 +/- 13.7 years) has detected signs of chronic hepatitis and hepatic cirrhosis, respectively, in 31 (71.4%) and 11 (26.2%) patients. "Dry syndrome" was diagnosed by criteria of European SS Study Group. LSG biopsy of the lower lip was conducted in 23 (54.7%) of 42 patients.The "dry" syndrome in CHC ran subclinically in 73.8% patients. Apparent symptoms of SS were seen primarily in middle-aged and aged women with CHC history over 10 years. The first signs of SS occurred in 25 (59.5%) patients 2.9 +/- 3.1 years prior to diagnosis of hepatic disease. All the patients had xerostomy. Xerophthalmia was recorded 1.5 times less frequently. In 16 (47.1%) patients with CHC "dry eye" and in 6 (17.6%) patients dry keratoconjunctivitis were detected. Pathohistological changes of LSG were diagnosed in 21 (91.3%) of 23 patients with CHC. In the majority of cases (86.9%) the glands exhibited insignificant inflammatory infiltration and advanced fibrosis. LSG in CHC is characterized by fibrosis prevalence over cell infiltration. 83.3% CHC patients had SS and other extrahepatic lesions. SS was most evident in 28.6% CHC patients with cryoglobulinemia.Registration of SS symptoms in CHC patients depends on targeted examination of patients with chronic HCV infection. The severity of the symptoms correlates directly with the infection duration and age of the patient. LSG lesions in CHC patients with SS are characterized by fibrosis pre-domination over cell infiltration.

To determine factors affecting overall survival and risk to develop hepatocellular carcinoma (HCC) in patients with hepatic cirrhosis (HC) of mixed (viral, alcoholic) etiology.Mono- and multi-variance analysis of prognostic effects of such factors as age of the patients, mixed infection VHB/VHC, markers of HBV replication, antibodies to nuclear antigen of HBV (HBcAb) without HBs-system in the serum ("isolated" HBcAb), duration of viral infection, alcohol intake and abuse, dilatation of the esophageal veins, some laboratory parameters were studied in 55 HC patients having at least one marker of hepatitis B virus (HBV) and/or hepatitis C virus (HCV), long history of alcohol abuse.It was found that risk of HCC was associated with duration of alcohol abuse and infection, mixed HBV/HCV infection, age 60 and older. Of independent significance was only duration of alcohol abuse. Lethal outcomes in HC patients in the mixed infection were due to development of HCC (36%) and HC complications (64%). Survival of the patients was less in severe dilatation of the esophageal veins, high clinicolaboratory index, low level of serum albumin, presence of "isolated" BcAb and mixed viral infection.Of the greatest prognostic efficacy in respect of survival was the model combining "isolated" HBcAb, the degree of esophageal veins dilatation and hepatitis activity.

Upon analysis of 550 cases of different chronic diffuse pulmonary diseases included in a group of interstitial diseases of the lungs (IDL) the authors came to the conclusion that IDL incorporate such variants as alveolitis, pulmonary vasculitis and pulmonary hemorrhages; granulomatosis covers exogenic allergic alveolitis, alveolitis in chronic active hepatitis; vasculitis group includes such rare diseases as necrotizing sarcoid granulomatosis vasculitis and lymphoid granulomatosis; fibrosing alveolitis--secondary alveolitis in sclerodermia systematica, rheumatoid arthritis, Sjogren's disease, chronic active hepatitis. Knowledge of IDL etiology (environmental, occupational, induced by radionuclides, drugs, viruses, fungi) with focus on drug affection of the lungs is thought of value. Biopsy and bronchial lavage findings are compared clinically and morphologically. Mechanisms of pulmonary fibrosis and approaches to inhibition of pulmonary fibrosis progression are outlined.

Various profiles of serum HBV markers (HbsAg) were identified in 16 patients, markers of active replication in 4 patients (HbeAg, 2 cases; HBcAb IgM, 1 case; HBcAb IgM and HbsAg IgM, 1 case) out of 22 patients with Sjögren disease (SD) having serum HBV markers and systemic manifestations. Of these 3 had a history of acute viral hepatitis, 12 were previously at risk to be infected with hepatitis viruses, 7 had neither the disease nor its risk factors, none of them had chronic active hepatitis or hepatic cirrhosis, 7 exhibited clinical signs of pseudolymphoma, 1 had serum monoclonal IgM kappa in the presence of HBV active replication markers (HBsAg IgM, HbcAb IgM). The present and previous data (on association of SS with chronic active hepatitis and hepatic cirrhosis due to HBV) suggest the involvement of the virus in SD etiology.

The authors describe pulmonary granulomatosis in a male patient with chronic active hepatitis of viral etiology with persistence of hepatitis B virus in blood serum and liver tissue. The presence of active virus infection with proven hepatitis B virus replication, evidenced by demonstration of HBeAg and HBcAb in blood serum, suggests an importance of universal etiological factor in the development of liver and lung lesions in the given patient, which is confirmed indirectly by demonstration of HBsAg in the cells of lavage fluid.

Different patterns of serum HBV markers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) were identified in 82 patients (12 with chronic active hepatitis, 67 with hepato-cirrhosis developing in the outcome of chronic active hepatitis, and in 3 with primary biliary cirrhosis) of 105 (78%) patients with chronic liver diseases. Besides, IgM HBcAb were identified in 9 of 47 patients (19.1%), HBsAg IgM in 4 of 9 patients (44.4%), antibodies to the delta-agent in 8 of 23 (34.8%) suffering from chronic liver diseases with the presence of serum HBV markers. Chronic liver diseases with the presence of HBsAg and/or other serum HBV markers were characterized by a variety of clinico-laboratory manifestations determined by the involvement of some organs and systems in a process. A degree of activity of chronic liver diseases was not correlated with a replication phase, an integration phase, and an immunological resolution phase in 49 patients with identified phases of development of HBV-infection. More frequent identification of serum HBV markers including those of a replication phase was not noticed among patients on prolonged immunosuppressant therapy.

Based on examination of 144 patients with chronic active hepatitis (CAH) and liver cirrhosis (LC) with a history of acute virus hepatitis (AVH) it was established that chronic progressive liver injuries of virus etiology with and without HB-antigenemia are characterized by the diversity of the clinico-laboratory findings determined by the involvement, in addition to the liver, of many organs and systems. The following variants of chronic AVH were recognized: (1) early development of chronic progressive liver injury due to AVH (40.4% of cases); (2) late occurrence of chronic progressive liver injury after a latent period of varying duration, namely up to 21-30 years and more (59% of cases). Late recognition of CAH and LC in patients with a history of AVH was caused, on the one hand, by a high rate of chronic progressive liver injuries after a long-term period, and on the other hand, by erroneous evaluation of extrahepatic lesions, which were the first symptoms of a chronic condition in many patients. Hepatitis virus B markers were detected in the blood serum of 44.5% of patients with CAH and LC with a history of AVH, mostly in men (55.3%) versus women (34.9%). In view of the difficulties of verifying liver injuries of virus etiology based on the laboratory research methods alone, one should be guided by a clinico-epidemiological approach to a study of CAH and LC etiology.