Genotype Distribution and Characteristics of Chronic Hepatitis C Infection in Estonia, Latvia, Lithuania, and Ukraine: The RESPOND-C Study.

Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode of viral transmission was blood transfusions (17.8%), followed by intravenous substance use (15.7%); however, in 50.9% of patients, the exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%), transmission by intravenous substance use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1-66.4%; GT3-28.1; and GT2-4.1%. The prevalence of GT1 was the highest in Latvia (84%) and the lowest in Ukraine (63%, p < 0.001). Liver fibrosis stages were distributed as follows: F0-12.2%, F1-26.3%, F2-23.5%, F3-17.1%, and F4-20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p < 0.001). Conclusions: This study contributes to the knowledge of epidemiologic characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

Hepatitis A virus subgenotypes in Latvia, 2008-2021.

BACKGROUND: In Latvia outbreaks of the HAV were observed between 2008 and early 2010 and again in 2017-2018. However, the risks of introducing and spreading infection still exist, as the virus spreads easily when personal hygiene is not followed. METHODS: To determine the spread of HAV subgenotypes in the territory of Latvia the VP1/P2A genomic region of HAV was amplified and sequenced for 259 case serum samples. The study carried out a molecular biological investigation and molecular epidemiological investigation. Demographic data (sex, age), disease data (hepatitis symptoms, hospitalization, vaccination) and epidemiology data (part of the outbreak, possible source of infection, recent travel) were collected. Based on the obtained sequences, the phylogenetic tree was built and analyzed for the homology and belonging to different isolated HAV clusters from other countries. RESULTS: From the obtained data, it was concluded that HAV subgenotype IA had 13 clusters and 12 sporadic cases, HAV subgenotype IB had eight clusters and 11 sporadic cases, HAV subgenotype IIIA had one cluster and nine sporadic cases. It was found that the sources of infection among the investigated cases were different, they were mostly associated with contact with a patient with HAV, travel, as well as between persons who inject drugs and men who have sex with men, and the prevalence of HAV similar sequences was observed in different years. It was concluded that patients with HAV subgenotype IA had the longest hospitalization duration and averaged 9.3 days, while patients with subgenotype IB - 7.3 days, subgenotype IIIA - 7.7 days. Analyzing the data on vaccination, it was found that mostly all were not vaccinated or had an unknown vaccination status. CONCLUSIONS: All of this has led to the conclusion that the application of molecular biological methods of the HAV and a careful analysis of epidemiological data can help to better understand the ways of spreading the infection, investigate local outbreaks, detect cases of imported infection and track the recirculation of the virus.

HCV Elimination in Central Europe with Particular Emphasis on Microelimination in Prisons.

In 2016, the WHO announced a plan to eliminate viral hepatitis as a public health threat by 2030. In this narrative review, experts from Bulgaria, Croatia, the Czech Republic, Hungary, Latvia, Lithuania, Poland and Slovakia assessed the feasibility of achieving the WHO 2030 target for HCV infections in Central Europe. They focused mainly on HCV micro-elimination in prisons, where the highest incidence of HCV infections is usually observed, and the impact of the COVID-19 pandemic on the detection and treatment of HCV infections. According to the presented estimates, almost 400,000 people remain infected with HCV in the analyzed countries. Interferon-free therapies are available ad libitum, but the number of patients treated annually in the last two years has halved compared to 2017-2019, mainly due to the COVID-19 pandemic. None of the countries analyzed had implemented a national HCV screening program or a prison screening program. The main reason is a lack of will at governmental and prison levels. None of the countries analyzed see any chance of meeting the WHO targets for removing viral hepatitis from the public threat list by 2030, unless barriers such as a lack of political will and a lack of screening programs are removed quickly.

Is elimination of HCV in 2030 realistic in Central Europe.

According to the recent data presented by Central-European HCV experts, the estimated prevalence of HCV is between 0.2% and 1.7% in certain countries in this region. There are no financial limitations to access to treatment in most countries. Patients in these countries have access to at least one pangenotypic regimen. The most common barriers to the elimination of HCV in Central Europe are a lack of established national screening programmes and limited political commitment to the elimination of HCV. Covid-19 has significantly affected the number of patients who have been diagnosed and treated, thus, delaying the potential elimination of HCV. These data suggest that the elimination of HCV elimination projected by WHO before 2030 will not be possible in the Central Europe.

How close are we to hepatitis C virus elimination in Central Europe?

AIM OF THE STUDY: To collect and analyse data obtained from HCV opinion leaders/experts from central European countries, on factors which can affect the WHO target of HCV elimination by 2030. MATERIAL AND METHODS: Data were collected from opinion leaders/experts involved in management of HCV infections in Central European countries which participated in 9th Conference of the Central European Hepatologic Collaboration (Warsaw, 10-11 October 2019). A dedicated questionnaire collected current information related to HCV elimination in Bulgaria, Croatia, the Czech Republic, Hungary, Latvia, Lithuania, Poland and Slovakia. RESULTS: The HCV prevalence rate in particular countries varied from 0.2% to 1.7%. In most central European countries all the HCV infected population is eligible for reimbursement of treatment. However, in some countries there are still some limitations related to the stage of the disease and people who inject drugs. All countries have access to at least one pangenotypic regimen. The most common barrier to HCV elimination in all countries is insufficient political will to establish priority for HCV. None of the reporting countries has established a national screening programme. CONCLUSIONS: Access to therapy for HCV is similar and the majority of patients in Central Europe can be treated according to the current guidelines. Unfortunately there are still some limitations and a lack of political will to implement national screening programmes. According to collected data HCV elimination will not be possible in the region by 2030.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Genetic variation spectrum in ATP7B gene identified in Latvian patients with Wilson disease.

BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by allelic variants in ATP7B gene. More than 500 distinct variants have been reported, the most common WD causing allelic variant in the patients from Central, Eastern, and Northern Europe is H1069Q. METHODS: All Latvian patients with clinically confirmed WD were screened for the most common mutation p.H1069Q by PCR Bi-PASA method. Direct DNA sequencing of gene ATP7B (all 21 exons) was performed for the patients with WD symptoms, being either heterozygous for H1069Q or without it on any allele. RESULTS: We identified 15 different allelic variants along with eight non-disease-causing allelic variants. Based on the gene molecular analysis and patients' clinical data variant p.His1069Gln was found in 66.9% of WD alleles. Wide clinical variability was observed among individuals with the same ATP7B genotype. The results of our study confirm that neurological manifestations of WD are typically present later than the liver disease but no significant association between the presence/absence of the most common genetic variant and mode of initial WD presentation or age at presentation was identified. CONCLUSIONS: (1) The most prevalent mutation in Latvian patients with Wilson disease was c.3207C>A (p.His1069Gln); (2) No significant phenotype-genotype correlation was found in Latvian patients with Wilson disease; (3) The estimated prevalence of Wilson disease in Latvia is 1 of 24,000 cases which is higher than frequently quoted prevalence of 1: 30,000.

Real-World Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir/+Dasabuvir±Ribavirin (OBV/PTV/r/+DSV±RBV) Therapy in Recurrent Hepatitis C Virus (HCV) Genotype 1 Infection Post-Liver Transplant: AMBER-CEE Study.

BACKGROUND The introduction of direct-acting antivirals (DAAs) has considerably improved therapeutic outcomes for patients with chronic hepatitis C virus (HCV) infections. The AMBER-CEE study aimed to assess real-world efficacy and safety of ombitasvir/paritaprevir/ritonavir/+ dasabuvir ±ribavirin (OBV/PTV/r/ +DSV±RBV) in the treatment of post-transplant recurrence of HCV infection. MATERIAL AND METHODS Liver transplant recipients with recurrent HCV genotype 1 infection, scheduled for OBV/PTV/r/+DSV±RBV according to therapeutic guidelines, were eligible. The primary efficacy endpoint was sustained virologic response (SVR) 12 weeks after the end of treatment (FU12). Clinical and laboratory adverse events (AEs) were recorded from baseline to FU12. RESULTS A total of 35 patients were included: 91.4% genotype 1b-infected, 94.3% treatment-experienced, and 77.1% at fibrosis stage ≥F2. SVR12 was achieved by all patients (35/35, 100%) including one patient with genotype 1a, one patient with detectable HCV RNA at the end of treatment, two patients with a history of first-generation DAA therapy, and two patients who prematurely discontinued the regimen. AEs were experienced by 22 patients (62.9%) and were mostly mild. No death, graft loss, or acute graft rejections were reported during the therapy. On-treatment hepatic decompensation occurred in three patients (8.6%). Anemia was observed in 29 patients (83.9%), with 21 (60%) requiring RBV dose reduction or discontinuation. CONCLUSIONS OBV/PTV/r/+DSV±RBV has excellent efficacy in post-transplant recurrence of HCV genotype 1-infection treated under real-world conditions. Excellent virologic outcomes were observed irrespective of prior treatment history or the degree of fibrosis, and AEs were mostly mild and transient.

Interleukin 28B Gene Polymorphism and Association with Chronic Hepatitis C Therapy Results in Latvia.

Introduction. With the standard treatment of chronic hepatitis C, sustained virological response (SVR) can be achieved only in half of all patients. Interleukin-28B appears to be involved in the control of HCV infection, and the genetic polymorphism of the encoding IL-28B gene may determine the efficacy of clearance of HCV. The aim of this paper was to detect IL-28B gene polymorphism in Latvia and to analyze therapy results. This is the first study on IL-28B gene polymorphism in Latvia. Material and Methods. There were 159 chronic viral hepatitis C patients included in the study. In order to detect IL-28B gene polymorphism, we used molecular biology techniques and methods: classical DNA separation, amplification by PCR, and standard sequencing. Genotype was defined as CC, CT, TC, or TT type. 142 patients were treated with the standard of care treatment. Results were analyzed according to IL-28B polymorphism. Results. There were 53 patients (33%) with CC genotype, 84 patients (53%) with CT/TC genotype, and 22 patients (14%) with TT genotype. 34 patients (74%) in CC genotype subgroup achieved SVR versus 50 patients (52%) in non-CC subgroups. In patients with genotype 1, SVR was achieved in 16 patients (84%) in CC subgroup versus 30 patients (47.6%) in non-CC subgroups, P = 0.007. Conclusions. The most common genotype of IL28B in Latvia is CT/TC, with an incidence of 53%. Patients with CC genotype achieved SVR more often than CT or TT subgroups. IL28B gene polymorphism therefore is a strong predictor of treatment result.

The prevalence of viral hepatitis C in Latvia: a population-based study.

BACKGROUND AND OBJECTIVE: Chronic viral hepatitis C (VHC) is one of the most discussed infectious diseases worldwide. The number of infected persons worldwide is approximately 170 million, and in Europe, it exceeds 9 million. The aim of this study was to determine the prevalence of antibodies to hepatitis C virus (anti-HCV prevalence) and prevalence of HCV viremia (HCV-RNA prevalence) in Latvia. MATERIAL AND METHODS: A multistage randomized selection was used. A total of 42 primary care physicians (PCPs) were randomly selected from the register of PCPs from different regions of Latvia. From each PCP register, 60 subjects were selected (1651 individuals in total) and invited for the anti-HCV test with a screening method (ELISA). In case of positive results, antibodies were confirmed by the Western blot test, and all these subjects were tested for HCV-RNA by polymerase chain reaction. RESULTS: Of the 1459 subjects tested, 57 were positive for anti-HCV (3.9%; 95% CI 3% to 5%); 35 of them were positive for anti-HCV with a confirmatory test (2.4%; 95% CI, 1.7% to 3.3%): 19 men and 16 women (3.8% and 1.7%, respectively; P=0.011). The results of HCV RNA test were positive in 25 subjects (1.7%; 95% CI, 1.2% to 2.5%): 15 men and 10 women (3% and 1% respectively, P=0.019). CONCLUSIONS: The prevalence of anti-HCV and HCV-RNA in Latvia was found to be 2.4% and 1.7%, respectively. The prevalence of anti-HCV and HCV-RNA was higher in men than women.