Understanding Covid-19: Digit ratios and duration of oxygen therapy in hospitalized Covid-19 patients.

BACKGROUND: Covid-19 severity shows a sex difference (males>females) and progressive hypoxia among the most seriously affected. Digit ratios are sexually dimorphic and may be negatively-related to prenatal (2nd-to-4th digits' ratio; 2D:4D) and pubertal (3rd-to-5th digits' ratio; 3D:5D) testosterone. Oxygen therapy is important in Covid-19 treatment and low 2D:4D is linked to efficient oxygen metabolism. We consider relationships between digit ratios and duration of oxygen treatment in hospitalized Covid-19 patients. METHODS: Digit lengths were measured from photographs of the patient's hands. Age, Sex, BMI, vaccination status and number of days of O2 treatment, were recorded. RESULTS: There were 100 (58 women) patients. Sex differences (males

Atherosclerotic cardiovascular disease risk profile of patients with chronic hepatitis B treated with tenofovir alafenamide or tenofovir disoproxil fumarate for 96 weeks.

BACKGROUND: Patients with chronic hepatitis B (CHB) who switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) show changes in lipid profiles. AIM: To evaluate how these changes affect cardiovascular risk. METHODS: This pooled analysis, based on two large prospective studies, evaluated fasting lipid profiles of patients with CHB who were treated with TAF 25 mg/day or TDF 300 mg/day for 96 weeks. Patients who fulfilled the American College of Cardiology criteria (age 40-79 years, high-density lipoprotein [HDL] 20-100 mg/dL, total cholesterol [TC] 130-320 mg/dL and systolic blood pressure 90-200 mmHg) required to assess 10-year atherosclerotic cardiovascular disease (ASCVD) risk with baseline lipid data and at least one post-baseline measurement were included in the ASCVD-risk population. The 10-year ASCVD risk was calculated for patients in this population, and changes from baseline to Week 96 were assessed using intermediate- (≥7.5%) and high-risk (≥20%) cut-offs. RESULTS: Among 1632 patients, 620 (38%) met the criteria for the ASCVD-risk population. At Week 96, fasting levels of all lipids, except TC:HDL ratio, were lower with TDF than TAF. No significant increase was observed in overall ASCVD risk or in any ASCVD-risk categories during the 96-week treatment period compared with baseline. A similar proportion of patients in the TAF and TDF treatment groups (1.3% and 2.3%, respectively; p = 0.34) reported cardiovascular events. CONCLUSION: Despite on-treatment differences in lipid profiles with TAF and TDF, predicted cardiovascular risk and clinical events were similar for both groups after 96 weeks.

Long-term Treatment With Tenofovir Alafenamide for Chronic Hepatitis B Results in High Rates of Viral Suppression and Favorable Renal and Bone Safety.

OBJECTIVES: Results from two Phase 3 studies, through 2 years, in chronic hepatitis B infection (CHB) showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. Here, we report updated results through 5 years. METHODS: Patients with HBeAg-negative or -positive CHB with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years. Efficacy (antiviral, biochemical, serologic), resistance (deep sequencing of polymerase/reverse transcriptase and phenotyping), and safety, including renal and bone parameters, were evaluated by pooled analyses. RESULTS: Of 1298 randomized and treated patients, 866 receiving TAF (DB and OL) and 432 receiving TDF with rollover to OL TAF at year 2 (n = 180; TDF→TAF3y) or year 3 (n = 202; TDF→TAF2y) were included. Fifty (4%) TDF patients who discontinued during DB were excluded. At year 5, 85%, 83%, and 90% achieved HBV DNA < 29 IU/mL (missing = failure) in the TAF, TDF→TAF3y, and TDF→TAF2y groups, respectively; no patient developed TAF or TDF resistance. Median eGFR (by Cockcroft-Gault) declined < 2.5 mL/min, and mean declines of < 1% in hip and spine bone mineral density were seen at year 5 in the TAF group; patients in the TDF→TAF groups had improvements in these parameters at year 5 after switching to OL TAF. CONCLUSIONS: Long-term TAF treatment resulted in high rates of viral suppression, no resistance, and favorable renal and bone safety.

Single-Nucleotide Polymorphisms in Base-Excision Repair-Related Genes Involved in the Risk of an Occurrence of Non-Alcoholic Fatty Liver Disease.

Oxidative stress is one of the pillars crucial in the development of a non-alcoholic fatty liver disease (NAFLD) and may cause DNA damage. Since the main pathway responsible for the repair of oxidative DNA damage is the base-excision repair (BER) pathway, we examined the relationship between the presence of different genetic variants of BER-associated genes and the risk of NAFLD. The study evaluates seven single nucleotide polymorphisms (SNPs) within five genes, hOGG1, APEX1, NEIL1, LIG3, LIG1, in 150 NAFLD patients and 340 healthy controls. The genotyping was performed using TaqMan probes and the results were presented as odds ratio with its corresponding 95% confidence interval. The following SNPs were assessed in the study: hOGG1 (rs1052133), APEX1 (rs176094 and rs1130409), NEIL1 (rs4462560), LIG3 (rs1052536), LIG3 (rs4796030), and LIG1 (rs20579). Four of the investigated SNPs, i.e., rs176094, rs1130409, rs4462560 and rs4796030, were found to be associated with NAFLD risk. Furthermore, the occurrence of insulin resistance in patients with steatosis depended on various LIG3 genetic variants. The findings imply the impact of genes involved in BER on NAFLD and fatty liver-related insulin sensitivity.

Indirect insulin resistance markers are associated with nonalcoholic fatty liver disease in type 1 diabetes.

INTRODUCTION: Insulin resistance (IR) in type 1 diabetes mellitus (T1DM) is associated with increased insulin dose requirements, poor glycemic control, and elevated risk of chronic complications. IR increases lipid synthesis and hepatic lipid content. Disruption in hepatic lipid accumulation and export leads to liver steatosis resulting in nonalcoholic liver disease (NAFLD). OBJECTIVES: The aim of the study was to explore the relationship between indirect IR markers and NAFLD in T1DM. PATIENTS AND METHODS: We analyzed 151 patients with T1DM (59 men, 92 women), with a median (interquartile range [IQR]) age of 40 (33-47) years and a median (IQR) diabetes duration of 19 (13-21)years. The median (IQR) value of glycated hemoglobin (HbA1c) was 7.5% (6.8%-8.%; 58 [51-66] mmol/mol). The following indirect IR markers were evaluated: estimated glucose distribution rate (eGDR), visceral adiposity index (VAI), and the triglyceride to high­density lipoprotein cholesterol ratio (TG/HDL­C). Fatty infiltration of the liver was quantified using transient elastography. Presence of NAFLD was defined as a controlled attenuation parameter value of 238 dB/m or greater. RESULTS: NAFLD was observed in 65 patients (43%). The participants with NAFLD were less insulin­sensitive (eGDR, 8.93 [6.39-9.97] vs 9.94 [8.09-11.13] mg/kg/min; P = 0.001; VAI, 1.52 [1.2-2.64] vs 1.34 [0.92-1.74]; P = 0.014; TG/HDL­C ratio, 1.35 [0.95-2.11] vs 1.11 [0.77-1.6]; P = 0.02) and were characterized by higher HbA1c values (7.75% [7.2%-8.4%] vs 7.3% [6.5%-8.1%]; 61 [55-68] vs 56 [48-65] mmol/mol; P = 0.02) than the patients without the disease. In a multivariable regression analysis adjusted for sex, diabetes duration, and HbA1c level, indirect IR markers were independently associated with NAFLD (eGDR: odds ratio [OR], 0.86; 95% CI, 0.77-0.97; P = 0.01; VAI: OR, 1.61; 95% CI, 1.05-2.49; P = 0.03, TG/HDL­C ratio: OR, 1.88; 95% CI, 1.11-3.18; P = 0.02). CONCLUSIONS: In T1DM, NAFLD is more likely to be found in individuals with lower insulin sensitivity.

Right-left digit ratios, a novel form of asymmetry: Patterns of instability in children and relationships to platelet counts and hospitalization in adults with COVID-19.

High right minus left (R-L) asymmetry of digit ratios has been reported to be linked to hospitalization for COVID-19. Here we examined the developmental patterns of this novel form of asymmetry in children and further explored their relationships to platelet counts and hospitalization for COVID-19 in adult patients. We considered ratios calculated from four digits (2D, 3D, 4D, 5D) in: (i) a sample of healthy participants aged 2 years to 18 years (n = 680, 340 males) and (ii) 96 adult patients (42 males) hospitalized for COVID-19 and 100 controls (53 males). The protocol for (ii) included a questionnaire and laboratory test results. In sample (i) of the six unsigned digit ratio asymmetries, those which included 5D had the highest mean asymmetry with the greatest between-individual variation and they were unstable over the age range of 2 years to 18 years. In sample (ii) patients showed higher asymmetries than controls in four ratios (2D:4D, 2D:5D, 3D:5D, 4D:5D) and a sum of asymmetries of the two independent ratios (2D:4D+3D:5D) correlated positively with platelet counts and hospitalization. Conclusion: Means and SDs of digit ratio asymmetry that include the 5th digit are high and age-unstable. Digit ratio asymmetry, particularly 5th digit ratio asymmetry and a composite measure of 2D:4D + 3D:5D asymmetry, may be positively linked to high platelet counts in COVID-19 patients and to an elevated risk of hospitalization.

The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease.

One of the most common chronic liver disorders, affecting mainly people in Western countries, is nonalcoholic fatty liver disease (NAFLD). Unfortunately, its pathophysiological mechanism is not fully understood, and no dedicated treatment is available. Simple steatosis can lead to nonalcoholic steatohepatitis and even to fibrosis, cancer, and cirrhosis of the liver. NAFLD very often occurs in parallel with type 2 diabetes mellitus and in obese people. Furthermore, it is much more likely to develop in patients with metabolic syndrome (MS), whose criteria include abdominal obesity, elevated blood triacylglycerol level, reduced high-density lipoprotein cholesterol level, increased blood pressure, and high fasting glucose. An important phenomenon in MS is also insulin resistance (IR), which is very common in NAFLD. Liver IR and NAFLD development are linked through an interaction between the accumulation of free fatty acids, hepatic inflammation, and increased oxidative stress. The liver is particularly exposed to elevated levels of reactive oxygen species due to a large number of mitochondria in hepatocytes. In these organelles, the main DNA repair pathway is base excision repair (BER). The present article will illustrate how impairment of BER may be related to the development of NAFLD.

MicroRNA profile and iron-related gene expression in hepatitis C-related hepatocellular carcinoma: a preliminary study.

INTRODUCTION: Hepatocellular carcinoma (HCC) is very difficult to diagnose, especially in its early stages. Non-invasive diagnostic and prognostic factors for this cancer are urgently needed. The purpose of our study was to investigate whether the microRNAs (miRNAs) regulating genes involved in iron homeostasis, whose disruption is a hallmark of HCC, offer potential as diagnostic or prognostic factors of HCV-related hepatocellular carcinoma. MATERIAL AND METHODS: Serum and tumor samples, and adjacent liver specimens, were obtained from 65 HCC patients. Additionally, serum samples were obtained from 65 healthy controls. In total, 28 circulating and eight tissue microRNA expression profiles were estimated by TaqMan qPCR. RESULTS: The expression profiles of all tested miRNAs were altered in the hepatocellular carcinoma patients. Iron level was negatively related to serum miR-96 level in healthy controls. Although the expression of iron metabolism proteins correlated with the level of serum miRNA in the controls, this was not observed in cancer patients. In the group of cancer patients, Let-7a, miR-29b, and miR-133a were positively related to ferroportin, transferrin and ferritin levels, while miR-31, miR-221 and miR-532 were negatively related to ferroportin, transferrin receptor 1 and ferritin levels. According to ROC curve analyses, 15 miRNAs are able to discriminate with 100% sensitivity and specificity between hepatocellular carcinoma patients and healthy subjects, which is more efficient than α-fetoprotein. CONCLUSIONS: Circulating miRNAs that regulate the expression of iron metabolism proteins should be evaluated as promising candidates for HCV-related HCC diagnostic agents.

Cardiovascular risk assessment by electrocardiographic Holter monitoring in patients with chronic hepatitis C.

INTRODUCTION: Cardiovascular diseases are ranked as the third cause of mortality among people infected with hepatitis C virus (HCV), but the relationship of infection with cardiovascular risk remains disputable. We have focused on the comprehensive use of parameters obtainable during long-term electrocardiographic (ECG) Holter monitoring. MATERIAL AND METHODS: Heart rate variability and turbulence (HRV and HRT), deceleration/acceleration capacity (DC/AC), corrected QT interval (QTc) and late potential (LP) were used. 36 persons were included, and 30 healthy subjects formed a control group. All were submitted to 24-hour Holter ECG-monitoring. RESULTS: The studied groups were not statistically significantly different with regards to basic anthropometric parameters. Statistically significantly higher medium and maximum heart rhythm and aminotransferase activities were recorded in patients with hepatitis C. The HRV parameters r-MSSD, p50NN, HF, and absolute DC/AC values were significantly lower in the subjects with hepatitis C than those in the control group. The QTc interval, measured for nocturnal hours, was also significantly longer in that group. There were no differences in the albumin level or basic echocardiographic parameters, including left ventricle ejection fraction. Nor was there any difference in the HRT parameters, or LP. The most interesting observation was the positive correlation among the number of viral RNA copies and DC, and LF. CONCLUSIONS: We confirmed the presence of autonomic disorders with prevalence of sympathetic system activity and prolonged QTc interval in patients with chronic hepatitis C. Those parameters significantly correlated with infection intensity. Our results suggest that HCV infection could be an independent cardiovascular risk factor, not associated with the lipid profile. Further prospective studies are needed.

Effect of comedication on ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin therapy in chronic hepatitis C - a real-world study.

AIM OF THE STUDY: This multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy. MATERIAL AND METHODS: Concomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool (http://www.hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used. RESULTS: Among the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic. CONCLUSIONS: Although most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions.

Forms of diagnostic material as sources of miRNA biomarkers in hepatocellular carcinoma: a preliminary study.

Aim: To assess the diagnostic value of selected miRNAs from various material collected from hepatocellular carcinoma (HCC) patients. Patients & methods: Tissue, serum, urine and fecal samples from HCC patients and healthy individuals were screened for associated miRNAs using microarray analysis; the selected miRNAs were then validated by real time-quantitative PCR on 65 patients. Results: Serum miR-122, a combination of serum miR-155 with miR-885-5p, a combination of urinary miR-532-3p with miR-765, and fecal miR-320a displayed 100% efficiency in discriminating patients from controls. A combination of urinary miR-532-3p and miR-765 allowed patients with neoplastic grade G3 to be distinguished from those with G1 and G2. Conclusion: Additionally to serum, urine and feces also appeared to be valuable source of potential HCC noninvasive miRNA biomarkers.

The Influence of Hepatitis C Virus Therapy on the DNA Base Excision Repair System of Peripheral Blood Mononuclear Cells.

Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage. The NE and ME obtained from patients before therapy demonstrated lower efficacy of 2'-deoxyuridine removal and DNA repair polymerization than those of the control group or patients after therapy. Moreover, the extracts from the patients after therapy had similar activity to those from the control group. However, the efficacy of apurinic/apyrimidinic site excision in NE did not differ between the studied groups. We postulate that infection of lymphocytes by the HCV can lead to a decrease in the activity of BER enzymes. However, the use of novel therapy results in the improvement of glycosylase activity as well as the regeneration of endonuclease and other crucial repair enzymes.

The Relationship Between Single-Nucleotide Polymorphisms, the Expression of DNA Damage Response Genes, and Hepatocellular Carcinoma in a Polish Population.

The molecular mechanism of hepatocellular carcinoma (HCC) is related to DNA damage caused by oxidative stress products induced by hepatitis B virus (HBV) or C (HCV) infection and exposure to environmental pollutants. Single-nucleotide polymorphisms (SNPs) of DNA damage response (DDR) genes may influence individual susceptibility to environmental risk factors and affect DNA repair efficacy, which, in turn, can influence the risk of HCC. The study evaluates a panel of 15 SNPs in 11 DDR genes (XRCC1, XRCC3, XPD, MUTYH, LIG1, LIG3, hOGG1, PARP1, NFIL1, FEN1, and APEX1) in 65 HCC patients, 50 HBV- and 50 HCV-infected non-cancerous patients, and 50 healthy controls. It also estimates the mRNA expression of nine DDR genes in cancerous and adjacent healthy liver tissues. Two of the investigated polymorphisms (rs1052133 and rs13181) were associated with HCC risk. For all investigated genes, the level of mRNA was significantly lower in HCC cancer tissue than in non-cancerous liver tissue. Seven of the investigated polymorphisms were statistically related to gene expression in cancer tissues. The disruption of DDR genes may be responsible for hepatocellular transformation in HCV-infected patients.

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.

Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study.

BACKGROUND & AIMS: Long-term treatment with tenofovir disoproxil fumarate (TDF) alone, or in combination with emtricitabine (FTC) is associated with sustained viral suppression in patients with lamivudine resistant (LAM-R) chronic hepatitis B (CHB). METHODS: LAM-R CHB patients were randomised 1:1 to receive TDF 300mg or FTC 200mg and TDF 300mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA<69IU/ml (<400copies/ml) at week 96 (primary efficacy endpoint) was reported previously. Here we present week 240 follow-up data. RESULTS: Overall, 280 patients were randomised to receive TDF (n=141) or FTC/TDF (n=139), and 85.4% completed 240weeks of treatment. At week 240, 83.0% of patients in the TDF arm, and 82.7% of patients in the FTC/TDF treatment arm had HBV DNA<69IU/ml (p=0.96). Rates of normal alanine aminotransferase (ALT) and normalised ALT were similar between groups (p=0.41 and p=0.97 respectively). Hepatitis B e antigen loss and seroconversion at week 240 were similar between groups, (p=0.41 and p=0.67 respectively). Overall, six patients achieved hepatitis B surface antigen (HBsAg) loss and one patient (FTC/TDF arm) had HBsAg seroconversion by week 240. No TDF resistance was observed up to week 240. Treatment was generally well tolerated, and renal events were mild and infrequent (∼8.6%). The mean change in bone mineral density at week 240 was -0.98% and -2.54% at the spine and hip, respectively. CONCLUSIONS: TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240weeks. LAY SUMMARY: The goal of oral antiviral treatment for chronic hepatitis B (CHB) is to achieve and maintain undetectable HBV DNA levels. Treatment options with enhanced potency, and low risk of resistance development for patients infected with lamivudine resistant (LAM-R) HBV are required. Tenofovir disoproxil fumarate (TDF) monotherapy was effective and well tolerated without TDF resistance development in CHB patients with LAM-R, for up to 240weeks. Clinical trial number: NCT00737568.

Non-sustained ventricular tachycardia during treatment of genotype 3 chronic hepatitis C - a case report.

UNLABELLED: More than 185 million people around the world have been infected with the hepatitis C virus (HCV), of whom 350 000 die each year. HCV is a now a curable disease, and advances in HCV therapy have resulted in steadily higher cure rates. Therapies based on PegINF are still treatment of choice. However PegINF can induce severe adverse events including cardiovascular disease. CASE REPORT: Here we report a 55 year old female patient with the severe hepatitis C and genotype 3 presented with recurring episodes of the loss of consciousness and palpitations in the course of therapy, combining interferon PegINF with ribavirin. During the diagnostics performed the occurrence of non-sustained ventricular. There were no other causes of arrhythmias, such as coronary heart disease or heart failure. It is considered that this is a result of treatment. Because of the confirmed viral clearance completed PegINF therapy at a lower dose, without further complications. CONCLUSIONS: The presented case of our patient illustrates very well the level of difficulty of the taken decisions, especially when treatment complications occurred, while also confirming the fairly assistive and supportive role of the non-invasive methods of cardiovascular diagnostics.

Epidemiology of hepatitis C virus infections in Lódzkie voivodeship / Epidemiologia zakazen HCV w województwie lódzkim

INTRODUCTION: Epidemiology of HCV subtypes plays an increasing role in treatment decision making in the era of direct acting antivirals. Data on incidence of HCV subtypes in Poland are sparse and equivocal. AIM OF THE STUDY: The aim of this study was to assess the distribution of HCV subtypes basing on data collected in Lodzkie province in 2015. MATERIALS AND METHODS: Patients with chronic hepatitis C were evaluated for antiviral treatment in one of the three infectious diseases departments in Lodzkie province in 2015 and had HCV genotype/subtype determined. The exclusion criteria were as follows: HBV and/or HIV coinfection and age under 18 years old. RESULTS: The study included 555 patients aged from 18 to 87 years. The rate of women was 52.8%, mean age was 47.4 years and treatment-experienced patients comprised 22.7% of study group. Genotypes 1, 3 and 4 were detected in 512 (92.25%), 34 (6.13%) and 7 (1.26%) patients, respectively. Subtype determination was performed in 464 patients infected with HCV genotype 1. The frequency of subtype 1a and 1b was 18.8% and 81%, respectively. Mean age in patients with HCV 1a infection was 28.6 years and was significantly lower than in patients infected with HCV 1b (52.5 years, p<0.05). A significant correlation between age and HCV subtype was observed. CONCLUSIONS: Prevalence of subtype 1a in patients with chronic hepatitis C in Lodzkie province is high, moreover, this subtype dominates in population of young adults (18-29 years).

Efficacy and direct costs of chronic hepatitis C treatment with first generation NS3/4A protease inhibitors in a real life population.

INTRODUCTION: Recent years have brought a significant advance in chronic hepatitis C (CHC) treatment that includes development of direct acting antivirals (DAA). Two of them, boceprevir (BOC) and telaprevir (TVR), were first approved for treatment of patients infected with CHC genotype 1 in combination with pegylated interferon (P) and ribavirin (R). Our aim was to evaluate the efficacy and direct costs of BOC/PR and TVR/PR in a real life population. MATERIAL AND METHODS: The study included adult patients qualified for the CHC Therapeutic Programme treated with TVR/PR or BOC/PR. Treatment was continued for 24 or 48 weeks. Sustained virological response, treatment discontinuation due to adverse events and lack of virological response rates were compared. RESULTS: A total of 243 adult patients with CHC were included. TVR/PR and BOC/PR were administered in respectively 122 and 121 patients. Thirty-two patients (13%) were treatment-naïve, whereas liver cirrhosis/advanced fibrosis was observed in 138 patients (56.7%). Overall, 43.6% of patients achieved a sustained virologic response (SVR). In the BOC/PR group the SVR rate was significantly lower than in the TVR/PR group (33.1% vs. 54.1%; p = 0.00094). Lack of response to therapy was observed in 41.3% and 12.3% of patients receiving BOC and TVR, respectively (p < 0.00001). The direct cost of achieving SVR in one patient was 285 450 PLN with BOC and 185 757 PLN with TVR. CONCLUSIONS: The very low treatment efficacy may be the result of inclusion criteria that allowed treatment of patients with advanced liver fibrosis/liver cirrhosis or previous treatment failure. Telaprevir seems to be significantly more potent against hepatitis C virus, with similar safety and tolerance.