A Rare Mutation in The APOB Gene Associated with Neurological Manifestations in Familial Hypobetalipoproteinemia.

Clinical phenotypes of familial hypobetalipoproteinemia (FHBL) are related to a number of defective apolipoprotein B (APOB) alleles. Fatty liver disease is a typical manifestation, but serious neurological symptoms can appear. In this study, genetic analysis of the APOB gene and ophthalmological diagnostics were performed for family members with FHBL. Five relatives with FHBL, including a proband who developed neurological disorders, were examined. A sequencing analysis of the whole coding region of the APOB gene, including flanking intronic regions, was performed using the next-generation sequencing (NGS) method. Electrophysiological ophthalmological examinations were also done. In the proband and his affected relatives, NGS identified the presence of the pathogenic, rare heterozygous splicing variant c.3696+1G>T. Two known heterozygous missense variants-c.2188G>A, p.(Val730Ile) and c.8353A>C, p.(Asn2785His)-in the APOB gene were also detected. In all patients, many ophthalmologic abnormalities in electrophysiological tests were also found. The identified splicing variant c.3696+1G>T can be associated with observed autosomal, dominant FHBL with coexisting neurological symptoms, and both identified missense variants could be excluded as the main cause of observed clinical signs, according to mutation databases and the literature. Electroretinography examination is a sensitive method for the detection of early neuropathy and should therefore be recommended for the care of patients with FHBL.

Effectiveness and safety of sofosbuvir-based therapy against chronic hepatitis C infection after successful kidney transplantation.

BACKGROUND: Direct-acting antivirals (DAAs), including sofosbuvir (SOF), are recommended for treatment of chronic hepatitis C virus (HCV) infection. However, few studies have investigated the effectiveness and safety of new DAAs in kidney transplant recipients (KTRs). OBJECTIVES: To assess the effectiveness and safety of SOF-based therapy in stable KTRs. PATIENTS AND METHODS: Forty KTRs were treated with SOF-based regimens. Rapid, end-therapeutic, and sustained virologic responses were assessed, as was liver stiffness by elastometry. Safety was monitored by measuring the estimated glomerular filtration rate (eGFR), blood hemoglobin (Hb) concentration, proteinuria, and blood trough levels of calcineurin inhibitors (CNIs). Other side effects were also recorded. RESULTS: The effectiveness of DAAs was 100% at all time points. The therapy did not significantly influence eGFR or proteinuria, but significantly decreased mean blood Hb levels (13.5 ± 2.0 vs 11.6 ± 1.9, respectively, P < 0.001), which required a dose reduction or cessation of ribavirin (RBV) in 50% of patients. A profound, significant decrease in initial CNI concentrations was also observed during treatment in the majority of patients within the first month of therapy. CONCLUSIONS: In this cohort of KTRs, the new SOF-based therapies were characterized by 100% effectiveness and good safety profiles. However, in patients co-treated with RBV, close blood Hb monitoring and early RBV dose reduction are necessary. In the majority of KTRs, antiviral therapy leads to a substantial and early decrease in CNIs levels, thus frequent measurement of CNI levels is necessary during SOF-based therapy.

Justified granulation aided noninvasive liver fibrosis classification system.

BACKGROUND: According to the World Health Organization 130-150 million (according to WHO) of people globally are chronically infected with hepatitis C virus. The virus is responsible for chronic hepatitis that ultimately may cause liver cirrhosis and death. The disease is progressive, however antiviral treatment may slow down or stop its development. Therefore, it is important to estimate the severity of liver fibrosis for diagnostic, therapeutic and prognostic purposes. Liver biopsy provides a high accuracy diagnosis, however it is painful and invasive procedure. Recently, we witness an outburst of non-invasive tests (biological and physical ones) aiming to define severity of liver fibrosis, but commonly used FibroTest®, according to an independent research, in some cases may have accuracy lower than 50 %. In this paper a data mining and classification technique is proposed to determine the stage of liver fibrosis using easily accessible laboratory data. METHODS: Research was carried out on archival records of routine laboratory blood tests (morphology, coagulation, biochemistry, protein electrophoresis) and histopathology records of liver biopsy as a reference value. As a result, the granular model was proposed, that contains a series of intervals representing influence of separate blood attributes on liver fibrosis stage. The model determines final diagnosis for a patient using aggregation method and voting procedure. The proposed solution is robust to missing or corrupted data. RESULTS: The results were obtained on data from 290 patients with hepatitis C virus collected over 6 years. The model has been validated using training and test data. The overall accuracy of the solution is equal to 67.9 %. The intermediate liver fibrosis stages are hard to distinguish, due to effectiveness of biopsy itself. Additionally, the method was verified against dataset obtained from 365 patients with liver disease of various etiologies. The model proved to be robust to new data. What is worth mentioning, the error rate in misclassification of the first stage and the last stage is below 6.5 % for all analyzed datasets. CONCLUSIONS: The proposed system supports the physician and defines the stage of liver fibrosis in chronic hepatitis C. The biggest advantage of the solution is a human-centric approach using intervals, which can be verified by a specialist, before giving the final decision. Moreover, it is robust to missing data. The system can be used as a powerful support tool for diagnosis in real treatment.

Eosinophilia in patient with acute cellular rejection after liver transplantation--case presentation and literature overview.

Acute cellular rejection (ACR) is still an important problem affecting patients after liver transplantation. Early diagnosis is necessary for initiate treatment, but there are not simple, noninvasive methods to confirm the diagnosis, and up to now, the gold standard in the evaluation of ACR is liver biopsy. The blood eosinophilia seems to be a promising tool supporting the diagnosis and monitoring the effectiveness of ACR treatment in patients after liver transplantation. In this paper a young patient transplanted due to primary sclerosing cholagitis with blood and graft eosinophilia is presented. Based on this interesting case, the literature overview is presented. We conclude that blood eosinophilia, especially with concomitant increase of gamma-glutamyl transpeptidase activity and bilirubin concentration could be an effective tool to predict ACR and may help to choose the.

[Respiratory function impairment during treatment of chronic hepatitis C with peginterferon alfa2 and ribavirin. Two cases presentation]. / Zaburzenia czynnosci ukladu oddechowego podczas leczenia przewleklego zapalenia watroby typu C pegylowanym interferonem i rybawiryna. Prezentacja przypadków.

Pulmonary complications during standard therapy of chronic hepatitis C with pegylated interferon and ribavirin are rare but connected with wide spectrum of diseases from sarcoidosis to interstitial pneumonitis. The clinical course of that complications is often serious. In this paper, presentation of two patients with chronic hepatitis C with different anamnesis was shown. In the first case, without pulmonary burden, during therapy the features of pneumonitis were developed. In the second case, in patient with sarcoidosis, the antiviral therapy was carried out without important pulmonary aggravation. In reference to these observations and based on available literature, the pathogenetic mechanisms underlying pulmonary complications during this kind of therapy were discussed. Additionally, the scheme of pulmonary diagnostic proceeding in patients certified and then treated with peginterferon and ribawirin was proposed.

[Changes in food preferences in pregnant women]. / Zmiana upodoban pokarmowych u kobiet w ciazy.

INTRODUCTION: Pregnant women frequently show significant changes in their eating habits. The aim of the study was to evaluate the pleasure derived from the consumption of selected food groups in women during the first and second trimester of pregnancy. MATERIAL AND METHODS: The studied group included 64 healthy women, aged 23-38. 32 women were in the first trimester of pregnancy and 32 women in the second trimester. The food preference interviews were conducted by the presentation of colourful photographs showing selected food groups. Then each participant answered the following question: "How much pleasure do you take from this food?". The results were recorded on a linear analogue scale. The women evaluated the pleasure they derived from food before pregnancy and in the first or second trimester of pregnancy. RESULTS: The women in the first trimester of pregnancy, showed a lower preference for eggs, sweets, pasta, red meat, fast food, salty snacks, spicy food, and seafood as compared to their preferences before the pregnancy. The women in the second trimester declared a significantly higher preference for chicken soup, fruit and sour food, and rated the taste of beef and pork, spicy food and salty snacks as less pleasurable than before the pregnancy. CONCLUSIONS: The first trimester of pregnancy is a period of decreased pleasure derived from food, whereas the perception of food in the second trimester is characterized by a general hedonic dimension similar to that from before the pregnancy. Both in the first and the second trimester of pregnancy women show a lower preference for beef and pork, spicy food and salty snacks.

Increased EBV DNAemia after Anti-SARS-CoV-2 Vaccination in Solid Organ Transplants.

The reactivation of latent viruses during SARS-CoV-2 infection is well recognized, and coinfection with Epstein−Barr virus (EBV) has been associated with severe clinical cases of COVID-19 infection. In transplant patients, EBV infection presents a significant challenge. Assessing the potential impact of SARS-CoV-2 vaccinations on EBV infections in stable kidney and liver transplant recipients was the objective of our study. Ten solid-organ-transplant (SOT) patients (eight kidney and two liver) vaccinated with standard doses of mRNA COVID-19 vaccines were included. EBV DNA viral load measurements were conducted prior to the vaccination and during a follow-up period (at the first month and after six months) after the second vaccine dose. After the second dose, a significant increase in median viremia was observed (p < 0.01) in 9 patients, and in one patient, the reactivation of EBV infection was found. Six months later, the median viremia decreased significantly (p < 0.05). The EBV viral load should be closely monitored as it could lead to the earlier diagnosis and treatment of EBV-related complications. Despite experiencing a decrease in the viral load six months post-vaccination, some patients still had a viral load over the baseline, which increased the risk of potential complications.

Significant Decrease in the Prevalence of Anxiety and Depression after Hepatitis C Eradication.

Chronic hepatitis C (CHC) is an ongoing epidemiological problem. The hepatitis C virus (HCV) may infect brain tissue, worsening mental health outcomes. The new era of highly effective oral Direct-Acting Agents (DAA) has brought a chance to eradicate the infection by 2030, however, screening campaigns are urgently needed as the majority of the infected are still undiagnosed. The aim of this study was to assess the prevalence of anxiety and depression among HCV patients, and the correlation with health-related quality of life (HRQoL) in the real-world setting, before and after DAA treatment. Data on anxiety, depression, and HRQoL, were collected by using self-reported questionnaires in a single center in Poland. The study group involved 90 respondents, 50% female, with a mean age of 43.8 years. HCV eradication decreased anxiety prevalence from 30.4% to 19.1% and depression from 35.2% to 18.2%. Significant improvement in 3 out of 4 of the WHOQOL-BREF (TheWorld Health Organization Quality of Life-BREF) domains and 8 out of 10 of the HQLQv.2 domains was obtained. Anxiety diminished the somatic domain scores by 3.5 (p < 0.0001), psychological by 2.3 (p = 0.0062), social by 1.75 (p = 0.0008), and environmental by 2.68 points (p = 0.0029). Depression diminished the somatic domain scores by 3.79 (p < 0.001), psychological by 2.23 (p < 0.001), social by 1.84 (p < 0.001), and environmental by 2.42 points (p = 0.004). In the Hepatitis Quality of Life Questionnaire version 2 (HQLQ v.2), the presence of depression and/or anxiety-impaired mental health, physical health, well-being, and vitality. These results indicate the need for an active search for HCV-infective people, especially among patients in psychiatric and psychological care.

Clinical insights into the role of immunosuppression in solid organ transplant recipients with COVID-19.

INTRODUCTION: The COVID-19 pandemic has disproportionately affected patients who have undergone solid organ transplantation (SOT). OBJECTIVES: We aimed to assess a cohort of transplant recipients who developed COVID­19, with a focus on immunosuppressive regimen, blood tacrolimus levels, clinical course, and patient and graft outcomes. PATIENTS AND METHODS: During the first 12 months of the pandemic, we identified ambulatory SOT recipients, including kidney, liver, and heart transplant recipients, diagnosed with SARS­CoV­2 infection. Baseline and follow­up data on graft function, immunosuppression, and patient and graft outcomes were assessed. RESULTS: Of the 2091 ambulatory patients, we identified 201 transplant recipients (9.6%) with SARS­CoV­2 infection (kidney transplant, n = 112; heart transplant, n = 56; liver transplant, n = 33). Patients after recent kidney (during 2015-2020) or heart (during 2020) transplant were significantly more often diagnosed with COVID ­19 than patients with a longer time since transplant. Additionally, blood trough tacrolimus levels measured during or shortly after COVID­19 in 23 kidney graft recipients were significantly increased by a median of 76.1% (interquartile range, 47.4%-109.4%) relative to predose trough levels. However, liver function parameters were not elevated, necessitating a tacrolimus dose reduction in 73.9% of the patients. CONCLUSIONS: In our study, kidney transplant recipients showed significant disturbances of tacrolimus metabolism, which may account for kidney function worsening during COVID­19. Moreover, infection was more common in patients with recent kidney or heart transplant, which suggests that the level of immunosuppression may affect morbidity related to SARS­CoV­2 infection.

HCV resistance-associated substitutions following direct-acting antiviral therapy failure - Real-life data from Poland.

BACKGROUND: This study analysed the NS3 and NS5A mutation frequencies, persistence and drug susceptibility in a cohort of real-life patients, with failed hepatitis C virus (HCV) therapy following directly acting antiviral (DAA) treatment. METHODS: NS3/NS5A Sanger sequences from 105 patients infected with HCV genotype (G) 1a (6,5.7%), G1b (94,89.5%), G3a (4,3.8%), and G4 (1,1.0%) post DAA treatment failure were analysed. NS3 and NS5A resistance-associated substitutions (RASs) were identified using the geno2pheno algorithm and associated with clinical variables. Time trends were examined using logistic regression. RESULTS: NS5A RAS were found in 87.9% of sequences derived from patients exposed to this class of agents, whereas NS3 RAS was found in 59.1% of HCV protease-exposed subjects. The frequency of the NS3 RAS increased with fibrosis stage, from 40.0% among F0/F1 individuals to 81.8% among patients with liver cirrhosis (F4, p = 0.094). NS5A mutation frequencies were 7.6% for 28A/V/M, 10.6% for 30 K/Q/R, 42.4% for 31I/F/M/V, and 75.8% for 93H. For NS3, the most common RASs were 56F-23.7%, 168A/E/I/Y/T/V-14.0%, and 117H-5.4%. Susceptibility to glecaprevir/pibrentasvir, velpatasvir/voxlaprevir, and elbasvir/grazoprevir was retained in 92.9%, 43.4%, and, 25.3% of patients, respectively. The frequency of NS3 RAS decreased with time elapsed from failure to sampling (p = 0.034 for trend). NS5A RAS frequency remained stable over the 24-months. CONCLUSIONS: Following DAA treatment failure, NS5A and NS3 RASs were common with increasing frequency among patients with advanced liver disease. In most cases, despite the presence of RASs, susceptibility to DAA combinations with higher genetic barrier was retained.

Association between liver steatosis and angiogenesis in chronic hepatitis C.

BACKGROUND: The relationship between steatosis and angiogenesis in chronic hepatitis C (CHC) is unclear. AIM AND METHODS: The aim was to explain whether liver steatosis presence and its extent are associated with the number of new-formed blood vessels in lobules and portal tracts in CHC. 72 CHC patients infected with viral genotype 1b, 35 of whom had steatosis were evaluated. Monoclonal antibody anti-CD34 was used to identify new-formed blood vessels. RESULTS: Patients with steatosis had a significantly more advanced stage of fibrosis (p = 0.002) and higher inflammatory activity grade (p = 0.062). CD34 expression in portal tracts (CD34pt), lobules and fibrous septa (CD34lfs) and total (CD34) were significantly higher in patients with steatosis (p = 0.034; p = 0.021; p = 0.023, respectively). CD34, CD34pt and CD34lfs differed significantly between patients with various steatosis grade (p = 0.006; p = 0.009; p = 0.013, respectively). CD34 and CD34pt differed significantly between each steatosis grade whereas CD34lfs between grade 1 and 3. Fibrosis stage and inflammatory grade were positively associated with steatosis extent (p = 0.015; p = 0.003, respectively). CONCLUSIONS: Our observations suggest that extensive steatosis of liver parenchyma in CHC patients is associated with formation of new blood vessels in lobules and portal tracts. Understanding the relationship between steatosis, fibrosis and angiogenesis is therefore of great importance for the introduction of new therapeutic approaches and in the evaluation of CHC progression.

Taste disturbances during therapy with pegylated interferon-alpha 2b and ribavirin in patients with chronic hepatitis C.

INTRODUCTION: The effectiveness of current standard therapy of chronic hepatitis C with pegylated interferon-alpha and ribavirin is unsatisfactory and associated with a variety of side effects. In addition to common side effects, appetite disorders and weight loss are universal problems that lead to decreased quality of life. The causes of appetite disorders are not known. The aim of the present study was to evaluate the influence of pegylated interferon-alpha 2b and ribavirin therapy on taste sensitivity, hedonic perception of taste sensations, and food preferences. MATERIAL AND METHODS: Nineteen chronic hepatitis C patients infected with genotype 1 HCV participated in the study. All patients received combined therapy with pegylated interferon-alpha 2b and ribavirin in adequate doses. The study included gustatory tests (taste recognition threshold and taste intensity with hedonic perception) using a gustometric method and an evaluation of the pleasure derived from eating. All examinations were performed before therapy and during the thirteenth week of therapy. RESULTS: After 12 weeks of therapy, patient sensitivity to salty and sweet was significantly decreased (p < 0.05), and bitter was described as being more unpleasant than before the therapy (p < 0.05). Also, the therapy decreased appetite without significant changes in patients' food preferences. CONCLUSIONS: We found multidirectional taste disturbances during treatment with pegylated interferon and ribavirin. The results may be useful in determining the role of taste in the development of appetite disorders in chronic hepatitis C patients treated with pegylated interferon and ribavirin.

Changes in Office Blood Pressure Control, Augmentation Index, and Liver Steatosis in Kidney Transplant Patients after Successful Hepatitis C Infection Treatment with Direct Antiviral Agents.

Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) can be successfully treated with direct antiviral agents (DAA). The aim of our study was to analyze different measures of vascular function during and after the DAA treatment. As we have observed the improvement of blood pressure (BP) control in some individuals, we have conducted an analysis of potential explanatory mechanisms behind this finding. Twenty-eight adult KTRs were prospectively evaluated before and 15 months after start of DAA therapy. Attended office BP (OBP), augmentation index (AIx), pulse wave velocity (PWV), flow-mediated dilation (FMD), liver stiffness measurement (LSM), and liver steatosis assessment (controlled attenuation parameter (CAP)) were measured. In half of the patients, improvement of OBP control (decline of systolic BP by at least 20 mmHg or reduction of the number of antihypertensive drugs used) and parallel central aortic pressure parameters, including AIx, was observed. There was a significant decrease in CAP mean values (241 ± 54 vs. 209 ± 30 dB/m, p < 0.05) only in patients with OBP control improvement. Half of our KTRs cohort after successful HCV eradication noted clinically important improvement of both OBP control and central aortic pressure parameters, including AIx. The concomitant decrease of liver steatosis was observed only in the subgroup of patients with improvement of blood pressure control.

Gastric myoelectrical activity in patients with primary biliary cirrhosis.

OBJECTIVE: To examine gastric myoelectrical activity in patients with primary biliary cirrhosis (PBC). MATERIALS AND METHODS: The study comprised 11 female PBC patients (average age 53.4 years, range 43-70) and two aged-matched control groups: 11 (53.4 years, range 37-78) healthy women, and 10 female patients with chronic hepatitis C, CHC (53.9 years, range 35-66), who were examined prior to administration of an antiviral therapy. Every subject underwent an electrogastrographic recording comprising a 30-min interdigestive and a 120-min postprandial period. RESULTS: Abnormal electrogastrograms, containing prolonged epochs of tachygastria in the postprandial phase were found in 2 out of 11 (18.2%) patients having both stage IV of the Scheuer's PBC classification, as well as in 1 patient out of 10 (10%) with CHC at stage F2 according to the METAVIR fibrosis score. CONCLUSION: Electrogastrographic abnormalities do not seem to be pathognomonic for the PBC as a disease, but rather would be considered an unspecific sequel of a morbid liver affection.

[Assessment of prevalence of intrapulmonary arterio-venous shunt in cirrhotic patients qualified to liver transplantation]. / Czestosc wystepowania plucnego przecieku krwi u chorych z marskoscia watroby kwalifikowanych do leczenia transplantacyjnego.

INTRODUCTION: Hepatopulmonary syndrome (HPS) is the clinical relationship between hepatic dysfunction and the arterial hypoxygenation caused by significant intrapulmonary arteriovenous blood leakage. HPS is responsible for increased peritransplant mortality. Data on prevalence of HPS are contradictory and its clinical risk factors are still unknown. Aim of the study was assessment of prevalence of HPS in cirrhotic patients qualified to liver transplantation and determination of clinical risk factors of this syndrome. MATERIAL AND METHODS: The study involved 30 patients with advanced liver cirrhosis of different etiology, qualified to liver transplantation. In all patients the laboratory hepatic examinations, pulmonary function tests (spirometry, gasometry) and albumin lungs-brain scintigraphy were performed. RESULTS: We did not find symptomatic HPS in the investigated group, but 2 patients (6.6%) with alcoholic cirrhosis showed arterio-venous intrapulmonary shunt. No significant differences in demographic and clinical data were found between patients with and without intrapulmonary shunt. CONCLUSIONS: Symptomatic HPS is rare complication of advanced cirrhosis. Symptom free intrapulmonary shunt occurs in less than 10% of patients, however, significance and clinical risk factors of this phenomenon remain unknown.

Effectiveness and safety of ledipasvir/sofosbuvir±ribavirin in the treatment of HCV infection: The real-world HARVEST study.

BACKGROUND: To evaluate the effectiveness and safety of ledipasvir/sofosbuvir (LDV/SOF)±ribavirin (RBV) regimen in a real-world setting. METHODS: Patients received a fixed-dose combination tablet containing LDV and SOF with or without RBV, for 8, 12 or 24 weeks. Patients were assessed at baseline, end of treatment, and 12 weeks after the end of treatment. The primary effectiveness endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: Of the 86 patients, aged 20-80 years, 82.6% were HCV genotype 1b-infected and 50.0% were cirrhotic. More than half (52.3%) had previously followed pegylated interferon-containing (PEG-IFN) treatment regimens, and 38.5% were null-responders. SVR12 was achieved by 94.2% of patients. All non-responders were cirrhotic: two demonstrated virologic breakthrough and the remaining three relapsed. All patients treated with an 8-week regimen achieved SVR12 despite having high viral load at baseline (HCV RNA of >1 million IU/mL in 8/10 patients, including one with a viral load of >6 million IU/mL). Adverse events were generally mild and transient. Most frequently, fatigue (22.1%), headache (15.1%), and arthralgia (7.0%) were observed. Laboratory abnormalities included anemia and hyperbilirubinemia. CONCLUSIONS: Treatment with LDV/SOF±RBV is an effective and safe option for patients with HCV, including those with advanced liver disease or a history of non-response to PEG-IFN-based therapy.

A novel approach to genome-wide association analysis identifies genetic associations with primary biliary cholangitis and primary sclerosing cholangitis in Polish patients.

BACKGROUND: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population. METHODS: Subjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays. RESULTS: Nineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance (P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously associated with PBC and PSC, respectively. The SNP, rs35730843, mapping to the POLR2G gene promoter (P = 1.2 × 10-5, OR = 0.39) demonstrated the highest effect size, and was protective for PBC, whereas for PSC respective SNPs were: rs13191240 in the intron of ADGRB3 gene (P = 0.0095, OR = 0.2) and rs3822659 (P = 0.0051, OR = 0.236) along with rs9686714 (P = 0.00077, OR = 0.2), both located in the WWC1 gene. CONCLUSIONS: Our cost-effective GWAS approach followed by individual genotyping confirmed several previously identified associations and discovered new susceptibility loci associated with PBC and/or PSC in Polish patients. However, further functional studies are warranted to understand the roles of these newly identified variants in the development of the two disorders.

Efficacy of HCV treatment in Poland at the turn of the interferon era - the EpiTer study.

THE AIM OF THE STUDY: Was to analyze the efficacy achieved with regimens available for chronic hepatitis C (CHC) in Poland between 2013 and 2016. MATERIAL AND METHODS: Data were collected from 29 centers and included 6786 patients with available sustained virologic response (SVR) data between 1 January 2013 and 31 March 2016. RESULTS: The sustained virologic response rate for genotypes (G) 1a, 1b, 2, 3 and 4 was 62%, 56%, 92%, 67% and 56% respectively; 71% patients (n = 4832) were treated with pegylated interferon α (Peg-IFNα) and ribavirin (RBV), with SVR rates of 58%, 49%, 92%, 67% and 55% respectively. The sustained virologic response among 5646 G1 infected patients was the lowest with natural interferon α (7%, n = 70) or PegIFN (50%, n = 3779) with RBV, and improved in those receiving triple regimens of Peg-IFN + RBV combined with boceprevir (47%, n = 485), telaprevir (64%, n = 805), simeprevir (73%, n = 132) or sofosbuvir (70%, n = 23). The sustained virologic response with interferon-free regimens of sofosbuvir and RBV (n = 7), sofosbuvir and simeprevir (n = 53), and ledipasvir and sofosbuvir (n = 64) achieved 86%, 89% and 94% respectively. The highest SVR of 98% was observed with ombitasvir/paritaprevir combined with dasabuvir (n = 227). Patients infected with G3 (n = 896) and G4 (n = 220) received mostly Peg-IFN + RBV with SVR of 67% and 56% respectively. Interferon-free regimens were administered in 18 G3/G4 patients and all achieved an SVR. Sofosbuvir combined with Peg-IFN and RBV was administered to 33 patients with an SVR rate of 94%, and a similar rate was achieved among 13 G2 patients treated with interferon and RBV. CONCLUSIONS: We observed significant differences in efficacy of HCV regimens available in Poland at the turn of the interferon era. The data will be useful as a comparison for therapeutic options expected in the next few years.

Prevalence of HCV genotypes in Poland - the EpiTer study.

THE AIM OF THE STUDY: Was to assess current prevalence of hepatitis C virus (HCV) genotypes in Poland, including their geographic distribution and changes in a given period of time. MATERIAL AND METHODS: Data were collected with questionnaires from 29 Polish centers and included data of patients diagnosed with HCV infection between 1 January 2013 and 31 March 2016. RESULTS: In total, data of 9800 patients were reported. The highest prevalence was estimated for genotype 1b (81.7%), followed by 3 (11.3%), 4 (3.5%), 1a (3.2%) and 2 (0.2%). Genotype 5 or 6 was reported in 6 patients only (0.1%). The highest prevalence of genotype 1 was observed in central (lódzkie, mazowieckie, swietokrzyskie), eastern (lubelskie) and southern (malopolskie, slaskie) Poland. The highest rate for genotype 3 was observed in south-western (dolnoslaskie, lubuskie) and eastern (podlaskie, warminsko-mazurskie and podkarpackie) Poland. Compared to historical data, we observed an increasing tendency of G1 prevalence from 72.0% in 2003 to 87.5% in 2016, which was accompanied by a decrease of G3 (17.9% vs. 9.1%) and G4 (9.0% vs. 3.1%). CONCLUSIONS: Almost 85% of patients with HCV in Poland are infected with genotype 1 (almost exclusively subgenotype 1b), and its prevalence shows an increasing tendency, accompanied by a decrease of genotypes 3 and 4.