Chronic lymphocytic leukemia/small lymphocytic lymphoma. Clinical recommendations

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.

Реактивация вируса гепатита В (HBV) у пациентов с лимфопролиферативными заболеваниями, получающих химиотерапию, может быть причиной развития фульминантной печеночной недостаточности и даже смерти при позднем распознавании и лечении HBV инфекции. Скрининг маркеров вирусов гепатита в группе больных онко-гематологическими заболеваниями является обязательным для клиницистов, практикующих лечение злокачественных опухолей. Обсуждаются способы профилактики и лечения реактивации HBV инфекции у больных с лимфомами.

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.

Heart injury is one of the extrahepatic manifestations of chronic hepatitis C (CHC). The paper gives Russian and foreign authors' data on a relationship between CHC and myocardial injury. It discusses different pathogenetic components (the direct effect of the virus, immunological components), through which hepatitis C virus can induce myocarditis and cardiomyopathies in patients with CHC.

We analysed the data of domestic andforeign authors on the relationship between hepatitis C and atherosclerosis. The possible role of the former condition as a risk factor of atherosclerosis even in very young patients is due to the properties of hepatitis C virus, mediators of inflammation, and metabolic disorders.

We analysed the data of domestic and foreign authors on the relationship between hepatitis C and atherosclerosis. The possible role of the former condition as a risk factor of atherosclerosis even in very young patients is due to the properties of hepatitis C virus, mediators of inflammation, and metabolic disorders.

Aim of investigation. To estimate relation of polymorphism of genes encoding reninangiotensin system components (AGT G-6A, AGT M235T and ATR1 A1166C) with rate of liver fibrosis progression in patients with chronic hepatitis C (CHC).Material and methods. Overall 109 patients with CHC and liver cirrhosis C with established stage of fibrosis and duration of disease have been divided into group of «rapidly progressing fibrosis» (55 patients, ≥0,130 fibrosis points/year) and «slowly progressing fibrosis» (54 persons, <0,130 fibrosis units/year). Assessment of polymorphism of studied genes was carried out by molecular genetic methods.Results. In CHC patients of «rapidly progressing fibrosis» group in comparison to «slowly progressing fibrosis» group minor A-allele (50,0 and 33,3% respectively, p=0,0126) and «mutant» АА-genotype (27,3 and 11,1%, р=0,0324; OR АА=3,00; 95% CI 1,07-8,45), AGT gene on locus G-6A, as well as minor T-allele (р=0,0407) of AGT gene in M235T locus were significantly more common while MM genotype of M235T polymorphism of AGT gene (20,8 and 44,4%, respectively, p=0,0090; OR MM=0,33; 95%-CI 0,15–0,73) were significant less frequent. No significant differences between groups in distribution of alternative alleles and genotypes of ATR1 gene on A1166C locus have been revealed.Conclusion. Carriage of mutant alleles of angiotensinogen gene on any of loci (G-6A or M235T) is the factor predicting more rapid progression of disease. As chronic hepatitis C is multifactorial disease, it is rational to use testing of allelic variants of angiotensinogen gene in patient-specific approach at CHC management.

AIM:To assess the association of the CYBA, NOS3, and MTHFR gene polymorphisms and a rate of fibrosis progression in chronic hepatitis C (CHC).SUBJECTS AND METHODS: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.RESULTS: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.CONCLUSION: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.

изменения в виде деструктивного негнойного холанги-та. В то же время у 9—19% больных с ПБЦ имеются се-рологические и/или морфологические признаки АИГ. Наблюдения, как правило, касаются перекреста лабо-раторных и серологических маркеров или гистологиче-ских признаков, свойственных АИГ и ПБЦ. Описания вариантных форм аутоиммунных заболеваний печени и системных заболеваний соединительной ткани встре-чаются редко.Мы наблюдали двух больных, длительное время страдавших системным заболеванием соединитель-ной ткани — БШ — с развитием вариантной формы АИГ — ПБЦ.Приводим клинические наблюдения.1. Больная 68 лет, инженер, инвалид II группы.В 1964 г. (в возрасте 22 года) появились рецидивиру-ющий конъюнктивит, сухость и ощущение песка в гла-зах, уменьшение количества слезной жидкости, сухость во рту. С 1970 г. присоединились рецидивы паротита, по-явился распространенный кариес с разрушением эмали зубов, эпизодически — субфебрилитет, сердцебиение, тремор кистей рук, увеличение СОЭ до 50 мм/ч.С 1974 г. больная находилась под наблюдением в НИИ ревматологии в связи с поздней стадией БШ с генерализованным сухим синдромом, постоянно полу-чала преднизолон (5—10 мг/сут). С середины 1970-х годов появились немотивированная нарастающая мы-шечная слабость вплоть до полной обездвиженности, выпадение волос, ломкость ногтей, упорный запор. Ди-агностирован аутоиммунный тиреоидит с явлениями гипотиреоза и гипотиреоидной миопатии, в связи с чем Известно, что основные аутоиммунные заболевания печени — аутоиммунный гепатит (АИГ), первичный билиарный цирроз печени (ПБЦ) и первичный скле-розирующий холангит (ПСХ) — нередко проявляют-ся рядом внепеченочных поражений, обусловленных также аутоиммунными реакциями [1—7]. При этом манифестация заболевания артралгиями, лихорадкой, миалгией или миопатией, полиневропатией, кожным геморрагическим васкулитом, сухим синдромом, по-ражением щитовидной железы, сердца, почек встре-чается у 20—40% пациентов [3, 6, 8]. У ряда больных отмечается сочетание аутоиммунного заболевания пе-чени (АИГ, ПБЦ, ПСХ) с системными заболеваниями соединительной ткани: системной красной волчан-кой (СКВ), ревматоидным артритом (РА), болезнью Шегрена (БШ), системной склеродермией, а также с CREST-синдромом или воспалительными заболевани-ями кишечника — язвенным колитом и болезнью Кро-на. В последние годы обращают внимание на наличие перекрестных или вариантных форм аутоиммунных заболеваний печени: АИГ—ПБЦ, АИГ—ПСХ [6—12]. Перекрестные синдромы между различными аутоим-мунными заболеваниями печени с одновременным вы-явлением клинических признаков, биохимических и серологических маркеров и гистологической картины в печени, свойственных двум заболеваниям, встречает-ся часто (18%) и труден для диагностики в связи с от-сутствием четких критериев и разграничений. У 5—8% больных с диагнозом АИГ имеются классические при-знаки ПБЦ: повышение уровня билирубина и щелоч-ной фосфатазы (ЩФ), характерные гистологические

Hepatic encephalopathy (PE) requires from physician to know all the aspects of its clinical manifestations and special psychometric methods for its diagnosis. Hepatic encephalopathy significantly reduces the quality of life in patients with chronic diffuse liver diseases. The article tells about early prescription of pathogenetic therapy to eliminate minor PE which is most common in patients with liver cirrhosis in order to prevent marked PE and improve the quality of life of patients and their survival.

Aim of investigation. To estimate frequency of late relapses and clinical outcomes in patients with chronic hepatitis C (CHC) with sustained virologic response (SVO) achievement at antiviral therapy (AVT).Material and methods. Overall 208 patients with CHC, including 12 at the stage of liver cirrhosis (LC), who achieved SVO were investigated. Mean duration of the follow-up was 56,1±35,4 months. Standard clinical and laboratory investigation and evaluation of RNA HCV was carried out. In 114 patients RNA HCV and DNA HBV in blood serum and peripheral mononuclear blood cells were studied by polymerase chain reaction (PCR) with fluorescent hybridization detection in «real time» mode (sensitivity of 10 IU/ml for HCV and 5 IU/ml for HBV).Results. In 3 (1,5%) patients late (i.e. over 6 months after AVT) relapses of HCV-infection were observed. Application of ultraresponsive PCR method allowed to reveal relapse half a year prior to its clinical and laboratory manifestation in 2 cases. No data on latent HCVinfection was obtained not in a single case, including patients with relapse of cryoglobulinemia syndrome. A principal cause of elevation of alanine transaminase activity was non-alcoholic steatohepatitis. In one LC patient development of esophageal varicose veins was detected. There were no cases of decompensation of LC, hepatocellular carcinoma and death due to liver disease.Conclusion. At patients who have achieved SVO as a result of AVT, late relapses of HCV-infection are rare and in the majority no disease progression was found. Relapses of cryoglobulinemia syndrome were observed, but data on presence of latent HCV-infection were not received. Highly sensitive PCR methods are rational for assessment of SVO.

Two clinical observations of the variant form of hepatic lesion: autoimmune hepatitis--primary biliary cirrhosis with systemic manifestations are presented in patients with long-standing Sjogren's syndrome, one at the stage of lever cirrhosis, the other at stage F2 of fibrosis. Difficulties encountered in diagnostics and the necessity of changing the entire spectrum of autoimmune markers characteristic of Sjogren's syndrome, autoimmune hepatitis and primary biliary cirrhosis are discussed. The possibility of different forms of hepatic lesions in autoimmune hepatitis--primary biliary cirrhosis is emphasized.

The presented clinical case gave rise to discussion of the main mechanisms and factors behind the progress of chronic hepatitis C. Special emphasis is laid on the currently available possibilities of antiviral therapy and its future prospects. The efficacy of personalized treatment and approaches to its improvement are considered based on the proper preventive measures and correction of factors responsible for poor responsiveness to the treatment, in the first place metabolic disorders (obesity, hepatic steatosis).