Effects of genetic polymorphism on the development of hepatocellular carcinoma in patients with metabolic-associated fatty liver disease. Review

Non‑alcoholic fatty liver disease (NAFLD) takes the first place among liver diseases in the countries with developed economies. In the year 2020, the group of experts proposed a new term, metabolic‑associated fatty liver disease, that allows to specify the diagnosis, to divide different NAFLD phenotypes and to optimize its treatment. The course of metabolic‑associated liver disease can range from mild forms (simple nonalcoholic steatosis, characterized by the accumulation of triglycerides in liver cells) up to an aggressive course with the development of cirrhosis and hepatocellular carcinoma (HCC). Aggressive course of the disease is observed in patients with type 2 diabetes mellitus, high body mass index, abdominal obesity and histologically confirmed steatohepatitis. Epidemiological and genetic studies have shown an association between the morphological stage of metabolic‑associated liver disease and hereditary factors. Progression to HCC is common in patients with severe steatohepatitis, although recent literature data showed a significant increase in the proportion of patients with F1/F2 fibrosis and НСС. This is due to the presence of metabolic syndrome and gene polymorphism. Three main genes can be singled out, the polymorphism of which is associated with the development of metabolic‑associated liver disease, insulin resistance, dyslipidemia, and fibrogenesis: PNPLA3, TM6SF2 and GCKR. Recently, an MBOAT7 gene polymorphism has been also identified, it peculiarly increases the risk of steatohepatitis development in patients who are alcohol abusers and/or have chronic viral hepatitis C. Detection of polymorphisms in these genes is useful for identifying groups at high risk for disease progression. Early diagnosis of HCC and risk stratification will allow to diagnose the disease at an early stage and optimize its treatment.

Epidemiological analysis of factors influencing the course of multidrug-resistant tuberculosis in HIV-infected patients with concomitant viral hepatitis

The epidemiological significance of combined forms of especially dangerous infections has not been studied enough, unlike mono-infections. Currently, there is a tendency towards an increase in the incidence of multidrug-resistant tuberculosis. The formation of severe forms of the disease is caused by other widespread infections, such as chronic viral hepatitis and HIV. Polymorbid conditions distort the clinical manifestations of tuberculosis, reduce the effectiveness of anti-tuberculosis therapy and worsen the prognosis of the disease. Risk factors among patients in this category need analysis to carefully monitor patients and ensure infection control. Objective is to analyze the factors affecting the course of multidrug-resistant tuberculosis in HIV-infected patients with concomitant viral hepatitis. Materials and methods. Cases of the combined pathology of multiresistant tuberculosis, HIV infection and viral hepatitis with a dominant diagnosis of tuberculosis are analyzed. Results and discussion. The influence of the immunological status on the course of combined pathology was revealed. Since all the patients under study had clinical stage 4 of HIV infection, tuberculosis developed as an opportunistic infection. Severe immunosuppression (CD4 < 200 cells/ml) contributed to the progression of the generalized tuberculosis process. Long-term immunodeficiency was an unfavorable factor; in the overwhelming majority of cases, antiretroviral therapy was prescribed only after tuberculosis was detected. The dependence of the clinical form of tuberculosis on the level of CD4-lymphocytes was noted: isolated lesion of the chest organs prevailed in patients with a level of CD4-lymphocytes more than 200 cells/ml, generalization of TB process — with CD4 less than 200 cells/ml. Patients with miliary tuberculosis had a higher mortality rate compared to patients with other clinical forms, regardless of antiretroviral therapy. It was revealed that socially disoriented young people with viral hepatitis C prevailed in the structure of patients, the prevalence of which was due to the influence of aggravating factors, such as alcohol and drug abuse, and stay in prisons. Against the background of combined treatment, there was no significant effect of viral hepatitis on the course of polymorbid conditions and the effectiveness of the therapy.

DEPENDENCE OF THE PHENOTYPIC COMPOSITION OF T-LYMPHOCYTES IN PATIENTS WITH CHRONIC VIRAL HEPATITIS C ON THE VIRUS GENOTYPE (IN DYNAMICS OF TREATMENT OF MEDICINES OF DIRECT ANTIVIRAL ACTION)

The aim of the study was to investigate the phenotype of effector T lymphocytes in patients with chronic viral hepatitis C (CVHC) in the dynamics of treatment with direct antiviral drugs depending on the genotype of the virus. 50 patients with CVHC were examined. The diagnosis was made on the basis of epidemiological and clinical laboratory data when specific serological markers of CHCV and RNA of hepatitis C virus (HCV) were detected. The determination of HCV RNA was carried out by the method of quantitative polymerase chain reaction in real time. The degree of liver fibrosis in patients with CVHC was assessed using ultrasound elastography. Patients were treated for 3 months with direct antiviral drugs according to the recommendations of the European Association for the Study of the Liver. The control group included 46 healthy donors with negative serological and molecular studies for the presence of viral hepatitis markers. The study of the subpopulation composition of helper and cytotoxic T-lymphocytes was carried out by direct immunofluorescence of whole peripheral blood. It was found that in CVHC patients were found characteristic features in the phenotypic composition of effector T-lymphocytes before and after treatment with direct antiviral drugs in depending on the genotype of HCV. The patients with HCV genotypes 1 and 3 had an increase in the content of terminal differentiated effector (TEMRA) T-helpers and effector memory (EM). Only patients with HCV genotype 2 had a decrease in the level of EM T-helper cells in the blood. A decrease in the relative number of T-helpers of central memory (СM) was independent of the HCV genotype. The level of effector subpopulations of cytotoxic T-lymphocytes in patients with CVHC was consistent with or exceeded control levels in depending on the genotype of HCV. The level of all investigated subpopulations of effector cytotoxic T-lymphocytes in patients with HCV genotype 1 is equal to the control values. The number of naive cytotoxic T cells and CM in peripheral blood in patients with HCV genotype 2 was increased. The content of naive cytotoxic T-lymphocytes, CM and TEMRA in patients with genotype 3 HCV in the blood was increased. The highest viral load was detected in patients with CVHC with genotype 1 HCV. Liver fibrosis was most pronounced in patients with CVHC infection with HCV genotypes 2 and 3. After 3 months of treatment with direct antiviral drugs the patients with CVHC had a reduced content of CM T-helpers regardless of the HCV genotype. In addition, patients with HCV genotypes 1 and 3 had a decrease in the number of naive T-helpers and patients with HCV genotypes 2 and 3 had a normalization of the content of naive cytotoxic T lymphocytes.

EFFECTIVENESS OF DIRECT-ACTING ANTIVIRAL DRUG THERAPY IN PATIENTS WITH CHRONIC VIRAL HEPATITIS C

All over the world hepatitis C is a global medical and social health problem, along with HIV infection, tuberculosis, hepatitis B, etc. According to the latest WHO estimates, the overall number of patients with chronic hepatitis C (CHC) in 2015 amounted to 71 million people (1 % of the world’s population). In Russia there are 5 million such patients. The largest number of people registered with CHC diagnosed in the Russian Federation is registered and lives in the Volga Federal District – 23.3 % (143,477 people). The incidence in the city of Ulyanovsk is very high (81.7 per 100 thousand of the population), and tends to grow steadily. The aim of this paper is to determine the effectiveness of 3D therapy in real clinical practice. Materials and Methods. Clinical charts of 151 patients with hepatitis C who underwent 8- and 12-week 3D and 3D+ ribavirin therapy (3 people) were analyzed. After therapy, the biochemical and virological responses were studied. The density of the liver tissue was determined on the FibriScanCompact 530 (Echosens, France). Results. There was a 100 % rate of sustained virological response to 8- and 12-week 3D therapy in complex groups of patients (extrahepatic manifestations, severe comorbid pathology, patients without previous responce to therapy). Triple therapy (Vikeira Pak) reduced the need for retreatment. Evaluation of interactions of direct antiviral drugs (3D scheme) in combination with ribavirin and without it was carried out with the most frequently prescribed drugs in the cohort of our patients. The 3D therapy regimen had a good safety profile: none of the patients cancelled treatment due to adverse events. Key words: chronic viral hepatitis C, 3D therapy, ombitasvir + paritaprevir + ritonavir, sustained virological response, genotype 1. Гепатит С является глобальной медико-социальной проблемой здравоохранения во всем мире наряду с такими заболеваниями, как ВИЧ-инфекция, туберкулез, гепатит В и ряд других инфекционных болезней. Согласно последним оценкам ВОЗ число больных хроническим гепатитом С (ХГС) в мире в 2015 г. составило 71 млн чел. (1 % населения Земли), из них 5 млн проживает в России. Наибольшее число лиц, состоящих на учете с диагнозом ХГС в РФ, зарегистрировано и проживает в Приволжском федеральном округе – 23,3 % (143 477 чел.). Заболеваемость в г. Ульяновске очень высока, составляет 81,7 на 100 тыс. населения и имеет тенденцию к неуклонному росту. Цель работы – определение эффективности 3D-терапии в реальной клинической практике. Материалы и методы. Проанализированы истории болезни 151 пациента с диагнозом «гепатит С». Все больные прошли курсы терапии 3D и 3D+рибавирин (3 чел.) в режиме 8 и 12 нед. Изучены биохимический, вирусологический ответы, после проведенного курса терапии определена плотность печеночной ткани на аппарате FibriScanCompact 530 (Echosens, Франция). Результаты. Доказана 100 % частота устойчивого вирусологического ответа на 8- и 12-недельные курсы 3D-терапии у сложных групп пациентов (с внепеченочными проявлениями, с тяжелой коморбидной патологией, у пациентов, ранее не отвечавших на терапию). Выбор трехкомпонентной терапии препаратом «Викейра Пак» обоснован возможностью снижения потребности в повторных курсах терапии. Оценка лекарственных взаимодействий препаратов прямого противовирусного действия схемы 3D в сочетании с рибавирином и без него производилась с наиболее часто назначаемыми препаратами в когорте наблюдаемых нами пациентов. Схема 3D-терапии имеет хороший профиль безопасности, ни один из пациентов не прекратил лечение в связи с нежелательными явлениями. Ключевые слова: хронический вирусный гепатит С, 3D-терапия, омбитасфир+паритапревир+ритонавир, устойчивый вирусологический ответ, генотип 1.

Continued low rates of HCV recurrence in HCV/HIV and HCV infected participants who achieved SVR after DAA treatment: Final results from the ACTG A5320 Viral Hepatitis C Infection Long-term Cohort Study (V-HICS)

Final results from the long-term VHICS cohort found low rates of HCV recurrence after DAA therapy in both HCV/HIV (0.67/100 p-y) and HCV (0.2/100 p-y) groups with over 500 person years of follow-up. Confirmed re-infections were in participants with HIV who reported high-risk behaviors.

Hepatitis C reinfection in former and active injecting drug users in Belgium

Background There is currently no systematic screening for hepatitis C (HCV) reinfection in people who inject drugs (PWID) after treatment in Belgium. However, in a recent meta-analysis, the overall HCV reinfection rate was 5.9/100 person-years (PY) among PWID. Accordingly, this study was undertaken to investigate the reinfection rate in former and active PWID who achieved the end of treatment response after direct-acting antiviral (DAA) treatment in Belgium. Methods This observational cross-sectional study recruited individuals with a history of injecting drug use who had achieved the end of treatment response to any DAA treatment between 2015 and 2020. Participants were offered a post-treatment HCV RNA test. Results Eighty-five potential participants were eligible to participate and contacted, of whom 60 participants were enrolled in the study with a median age of 51.0 (IQR 44.3–56.0) years; it was reported that 23.3% continued to inject drugs intravenously after DAA treatment. Liver cirrhosis was present in 12.9%. The majority had genotype 1a (51.7%) or genotype 3 (15.0%) infection. We detected no reinfections in this study population. The total time patients were followed up for reinfection in the study was 78.5 PY (median 1.0 years IQR 0.4–2.0). Conclusion Reinfection after successful treatment with DAA initially appears to be very low in Belgian PWID. Therefore, efforts should be made to screen individuals with persistent risk behaviors for reinfection systematically. In addition, a national HCV registry should be established to accurately define the burden of HCV infection and reinfection in Belgium and support the elimination of viral hepatitis C in Europe. Trial registration clinicaltrials.gov NCT04251572, Registered 5 Feb 2020–Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04251572.