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Leishmaniasis is a vector-born parasitic disease characterized by predominant cutaneous or visceral involvement with fever, hepatosplenomegaly and anemia. Leishmaniasis has relatively high prevalence in tropical and subtropical areas. Several sporadic and mostly imported cases are detected in Russian Federation. Nevertheless, some local incidents are noted in southern areas (Crimea, Dagestan). Lack of epidemiological alertness hampers confirmation of diagnosis and may lead to incorrect treatment. The article summarizes current state of knowledge in epidemiology, diagnostic approach and treatment of leishmaniasis. Particular clinical case is discussed.Лейшманиозы протозойные трансмиссивные заболевания, характеризующиеся преимущественным поражением внутренних органов (висцеральные лейшманиозы) или кожи (кожные лейшманиозы) с развитием лихорадки, спленомегалии и анемии. В Российской Федерации большинство зафиксированных случаев связано с посещением стран, эндемичных по лейшманиозу; в то же время имеются единичные сообщения о развитии заболевания у лиц, посетивших южные регионы России (Крым, Дагестан) и Закавказье или постоянно проживающих в них. Отсутствие настороженности со стороны клиницистов существенно затрудняет своевременную постановку правильного диагноза и может привести к выбору неверной тактики лечения. В статье рассмотрены современные представления об эпидемиологии, подходах к диагностике и лечению лейшманиоза; обсуждаются особенности представленного клинического случая.

To study liver function and portal hypertension, incidence and risk factors of liver-related complications, including hepatocellular carcinoma (HCC), in patients with HCV-related liver cirrhosis achieved sustained virologic response (SVR) after direct-acting antiviral therapy.Patients with HCV-related liver cirrhosis were followed up after achievement SVR with assessment of liver function parameters, portal hypertension, Model for End-stage Liver Disease (MELD) and Сhild Pugh (CP) scores, complications development, including HCC, every 36 months. The median follow-up duration was 24 [18; 30] months after end of treatment.At last observation, a number of cirrhotic patients with CP class A increased from 72% to 85%, with CP class B reduced from 23.5% to 12.5%, with CP class C from 4.5% to 2.5%. In 89% patients were identified a regress of liver fibrosis (from 23.5 [16.9; 28] to 15.0 [10.2; 21.3] kPa,p0.005), each third patient reduction of fibrosis stage to F2/F3. In 19 (9.5%) patients were occurred liver-related complications, including HCC (in 9 patients). Baseline high total bilirubin level (34 mol/l) (Hazard ratio (HR) 11.5, 95% confidence interval (CI) 2.357.8,р0.005) and ascites (HR=17.6, 95% CI 2.1144.8,p=0.008) were independent risk factors associated with HCC development.The risk of HCC development remains in patients with HCV-related liver cirrhosis, despite on eradication of hepatitis C virus. Therefore, these patients should continue to undergo more intensive examination (ultrasound examination and determination of alfa-fetoprotein level each 36 months), including contrast-enhanced methods of imaging, the frequency of which should be determined.Цель исследования.Изучение динамики показателей функции печени и портальной гипертензии, частоты и факторов риска развития осложнений, включая гепатоцеллюлярную карциному (ГЦК), у больных циррозом печени (ЦП) в исходе хронического гепатита С (ХГС) после достижения устойчивого вирусологического ответа (УВО) в результате лечения препаратами прямого противовирусного действия. Материалы и методы.У больных ЦП в исходе ХГС (n=200) после достижения УВО оценивали параметры портальной гипертензии, белково-синтетической функции печени, индексы MELD и ЧайлдаПью (ЧП), развитие осложнений ЦП, в том числе ГЦК, каждые 36 мес. Медиана наблюдения от окончания лечения составила 24 [18; 30] мес. Результаты.К концу наблюдения доля больных ЦП класса А по ЧП увеличилась с 72 до 85%, ЦП класса В по ЧП уменьшилась с 23,5 до 12,5%, ЦП класса С по ЧП с 4,5 до 2,5%. По данным эластометрии печени в 86% случаев наблюдался регресс фиброза с 23,5 [16,9; 28] до 15,0 [10,2; 21,3] кПа (p0,005), у каждого третьего больного уменьшение стадии фиброза печени до F2 или F3. У 19 (9,5%) больных отмечено развитие осложнений ЦП, включая ГЦК (n=9). По данным многофакторного регрессионного анализа Кокса независимыми факторами риска ГЦК оказались исходно более высокий уровень общего билирубина (34 мкмоль/л) [отношение шансов (ОШ) 11,5; 95% доверительный интервал (ДИ) 2,357,8;р0,005] и асцит (ОШ 17,6; 95% ДИ 2,1144,8;p=0,008). Заключение.У больных ЦП в исходе ХГС сохраняется риск развития ГЦК, несмотря на элиминацию ВГС. Необходимо более тщательное наблюдение (ультразвуковое исследование печени и определение альфа-фетопротеина сыворотки 1 раз в 36 мес), включая контрастные методы исследования, периодичность которых предстоит определить.

Exactly 30 years ago, hepatitis C virus was identified. Over the years, tremendous success has been achieved in the treatment of hepatitis C, which is currently considered to be an almost completely curable disease. The review presents the main stages in the development of hepatitis C antiviral therapy, the efficacy of various treatment regimens. The greatest progress in treatment was noted over the past 5 years when drugs with direct antiviral action appeared and began to be widely used, including in Russia, which ensure the elimination of the virus in 90-95% of cases.Ровно 30 лет назад был идентифицирован вирус гепатита С. За эти годы достигнут огромный успех в лечении гепатита С, который в настоящее время рассматривается как практически полностью излечимое заболевание. В обзоре представлены основные этапы становления противовирусной терапии гепатита С, эффективность различных схем лечения. Наибольший прогресс в лечении отмечен в течение последних 5 лет, когда появились и стали широко применяться, в том числе и в России, препараты с прямым противовирусным действием, которые обеспечивают элиминацию вируса в 90-95% случаев.

Nucleos(t)ide analogues are first-line therapies for the treatment of chronic hepatitis B. However, the efficacy and safety of long-term treatment and the necessary duration of therapy remains the subject of discussion. Aim. To assess the efficacy and safety of long-term treatment with nucleos(t)ide analogues in patients with chronic hepatitis B. Materials and methods. We conducted an observational study in 101 chronic hepatitis B (HBeAg-negative and HBeAg-positive) patients treated (3 years) with entecavir, tenofovir or telbivudine. Results and discussion. Treatment with entecavir and tenofovir was associated with high rate of virologic and biochemical response (95%) and HBeAg seroconversion (93% and 67%, respectively). Cumulative rate of virologic resistance was 0; 3.1% and 43.5% for tenofovir, entecavir and telbivudine, respectively. Long-term nucleos(t)ide analogues treatment resulted in a regress of liver fibrosis (from 8.92 to 7.18 kPa, р0.0001) and reduction in the number of patients with advanced fibrosis (from 48.1% to 13.8%, р0.0001). Entecavir and tenofovir were safe and well tolerated, while treatment with telbivudine was associated with development of myopathy in 13% of cases. Conclusion. Entecavir and tenofovir might be recommended for the treatment of chronic hepatitis B because of having potent antiviral effect, high genetic barriers against resistance and good safety.

Aim. To investigate risk factors of unfavorable prognosis in patients with chronic hepatitis C (CHC), including liver cirrhosis (LC), decompensated cirrhosis, hepatocellular carcinoma (HCC), cryoglobulinemic vasculitis (CryoVas) and B-cell non-Hodgkin’s lymphoma. Materials and methods. This was a retrospective study using data of 824 patients with CHC hospitalized between 2010 and 2016 in clinic named after E.M. Tareev. We used multivariate analysis including logistic regression to calculate odds ratios (ORs) for potential risk factors/predictors associated with unfavorable outcomes in patients with CHC. Results and discussion. The rate of LC, decompensated LC, HCC, serious CryoVas and B-cell lymphoma in patients with CHC was 39.1% (322/824), 14.0% (115/824), 2.8% (23/824), 5.2% (43/824) and 1.2% (10/824), respectively. After adjustment for sex and age the rate of LC, decompensated LC, HCC was 22.8, 8.0 and 1.5%, respectively. Annual rate of LC in patients with CHC was 1.5%; in cirrhotic patients annual rate of decompensated LC and HCC was 2.9 and 1%, respectively. Risk factors independently associated with development of LC were elevated body mass index (OR 1.43), immunosuppressive therapy (OR 1.67), diabetes type 2 (OR 2.03), absence of antiviral therapy (OR 2.15), alcohol abuse (OR 2.34), duration of infection ≥20 years (ОR 2.74) and an absence of sustained virological responce (SVR) (OR 2.98). Independent risk factors for decompensation in cirrhotic patients included diabetes type 2 (OR 1.47), alcohol abuse (OR 1.53), an absence of antiviral therapy (OR 2.36) and an absence of SVR (OR 1.94). An episode of decompensation was the independent predictor of HCC in cirrhotic patients (OR 3.99). Genotype 1b (OR 1.66) and an absence of antiviral therapy (OR 3.31) were independently associated with serious CryoVas. Two prognostic scales were offered for risk evaluation of LC and its complications. Conclusions. Multivariate analysis showed several factors independently associated with higher risk for LC, decompensation of LC, HCC, serious CryoVas in patients with CHC. The rate of unfavorable outcomes of CHC is found, including rare extrahepatic manifestations.

Clinical features of overlap autoimmune hepatitis/primary biliary cholangitis and morphological-proved sarcoid lesions (lungs, lymph nodes, skin) were performed. Data of long-term clinical observation presented in comparison with the results of laboratory datas, instrumental and morphological studies of liver tissue, lungs, skin. The modern aspects of pathogenesis of association autoimmune and granulomatous diseases arediscussed on the example of clinical cases of combination of cholestatic variants of autoimmune hepatitis and generalized sarcoidosis. Keywords: sarcoidosis, autoimmune hepatitis, primary biliary cholangitis, primary biliary cholangitis-autoimmune hepatitis-overlap, extrahepatic manifestations.

Previous short-term studies have reported on liver function improvements and delisting among liver transplantation (LT) candidates with hepatitis C virus (HCV) and decompensated liver cirrhosis after successful antiviral therapy. This study aimed to evaluate the long-term impact of HCV eradication on liver function, portal hypertension, probability of delisting, and clinical outcomes in patients awaiting LT.Forty-five LT candidates with decompensated HCV cirrhosis were prospectively observed after HCV eradication by direct-acting antiviral therapy. The median follow-up (FU) time was 24 months.Twenty-six (57.8%) patients were delisted due to clinical improvement. Multivariate analysis revealed male gender (hazard ratio (HR) 3.28; p = 0.022), baseline Child - Turcotte - Pugh class C (HR 4.81; p = 0.003), and delta prothrombin index2% between baseline and the time of sustained virological response (HR 3.82; p = 0.01) as independent risk factors for non-delisting. During a median FU of 21 months after delisting, hepatocellular carcinoma (HCC) developed in 2 (7.7%) patients. Among non-delisted patients, HCC developed in 6 (31.6%) cases, variceal bleeding developed in 3 (15.8%) patients, and spontaneous bacterial peritonitis developed in 2 (10.5%) patients.HCV eradication lead to the delisting of more than 50% of patients, but did not eliminate the HCC risk, and close monitoring of patients should continue after the end of treatment.

Despite very high efficacies of direct-acting antivirals (DAAs) reported in clinical trials, treatment failure in real-life practice can occur in 5–10% of cases and is mostly associated with emergence of resistance-associated substitutions (RASs). Little is known about the efficacy of retreatment in these patients, especially in those with decompensated cirrhosis, and only a few retreatment studies have been performed so far. Here we present case reports of successful sofosbuvir-based treatment in patients with advanced class B cirrhosis with prior pegylated interferon/ribavirin and all-oral DAA failure with multiclass drug resistance. HCV resistance testing at failure was performed to guide the choice of salvage therapy.

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).