Hepatitis C Infection as a Risk Factor for Hypertension and Cardiovascular Diseases: An EpiTer Multicenter Study.

Hepatitis C infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, more and more is being heard about extrahepatic manifestations of the hepatitis C infection including its possible influence on the development of hypertension and cardiovascular diseases. In the given work, the frequency analysis of the incidence of hypertension and cardiovascular diseases among 2898 HCV-infected patients treated in Poland and the assessment of their relevance to the HCV genotype and the progression of liver fibrosis can be found. The prevalence of hypertension in the group of analyzed patients was 39% and was significantly associated with old age (OR = 1.08 (1.07-1.08)) and female sex, as well as the progression of liver fibrosis (OR = 1.54 (1.29-1.85)). Hypertension was found in 47.6% of patients with F4 fibrosis, 42.1% of patients with F3 fibrosis, and 25% of patients with F1 fibrosis. The incidence of cardiovascular disease in the studied group of patients was as follows: all incidents, 131 (4.52%); including ischemic heart disease 104, (3.95%); stroke, 2 (0.07%); atherosclerosis, 21 (0.72%); and aneurysms, 4 (0.14%). The obtained results prove that the prevalence of cardiovascular diseases is significantly associated with the advanced age of patients and the progression of liver fibrosis. The relevance of sex and the HCV genotype to the prevalence frequency of cardiovascular diseases in the study group has not been proven. This being the case, no differences in the frequency of their incidence depending on the HCV genotype, including genotype 3, was found. Hepatitis C infection as a non-classical risk factor for cardiovascular disease and hypertension does require further studying.

HCV Genotype Has No Influence on the Incidence of Diabetes-EpiTer Multicentre Study.

HCV infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, one finds more and more extrahepatic manifestations of HCV infection, including its possible influence on the development of diabetes. In the presented work, one finds the frequency analysis of the incidence of diabetes among 2898 HCV infected patients treated in Poland, and the assessment of their relevance to the HCV genotype and the progression of fibrosis. The results indicate that the hepatitis C infection seems to be a risk factor for diabetes in persons with more advanced liver fibrosis, for older people, and for the male gender. Thus, one found no differences regarding the frequency of its incidence depending on HCV genotype, including genotype 3.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C: Data from the Polish EpiTer-2 cohort study.

BACKGROUND: The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C, making it highly effective and safe for patients. However, few researchers have analyzed the factors causing therapy failure in some patients. AIM: To analyze factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting. METHODS: The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020. Data collected from the online EpiTer-2 database included the following: hepatitis C virus (HCV) genotype, stage of fibrosis, hematology and liver function parameters, Child-Turcotte-Pugh and Model for End-stage Liver Disease scores, prior antiviral therapy, concomitant diseases, and drugs used in relation to hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) coinfections. Adverse events observed during the treatment and follow-up period were reported. Both standard and machine learning methods were used for statistical analysis. RESULTS: During analysis, 12614 patients with chronic hepatitis C were registered, of which 11938 (mean age: 52 years) had available sustained virologic response (SVR) data [11629 (97%) achieved SVR and 309 (3%) did not]. Most patients (78.1%) were infected with HCV genotype 1b. Liver cirrhosis was diagnosed in 2974 patients, while advanced fibrosis (F3) was diagnosed in 1717 patients. We included patients with features of hepatic failure at baseline [ascites in 142 (1.2%) and encephalopathy in 68 (0.6%) patients]. The most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index. Among viral factors, genotype 3 and viral load also exerted an influence on treatment efficacy. Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex, which was not confirmed by the multivariate analysis using the machine learning algorithm (random forest). Coinfection with HBV (including patients with on-treatment reactivation of HBV infection) or HIV, extrahepatic manifestations, and renal failure did not significantly affect the treatment efficacy. CONCLUSION: In patients with advanced liver disease, individualized therapy (testing for resistance-associated variants and response-guided treatment) should be considered to maximize the chance of achieving SVR.

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.

Recommendations for the treatment of hepatitis B in 2017.

The therapeutic goal which is currently unfrequent but realistic in HBV infected patients is sustained HBsAg clearance. It is preceded by the loss or significant suppression of HBV replication and leads to inhibition of the progression of liver fibrosis, normalization of biochemical indicators of liver damage, reduction in the risk of hepatocellular carcinoma, prolongation of survival, prevention of HBV infection in the transplanted organ in post-transplant patients, enhancement of the quality of life, inhibition or reversal of extrahepatic changes associated with HBV infection, and halting of the spread of HBV infections. Recommendations of Polish Group of Experts for HBV for 2017 provide guidelines to assess treatment eligibility, choice of the first-line drug, monitoring and duration of treatment, management of treatment failure as well as therapy of HBV associated cirrhosis or hepatocellular carcinoma. Moreover it contains advice for treatment of HBV infection in children, females planning pregnancy or pregnant. We also included recommendations for pre- and post-exposure prophylaxis, prevention of HBV transmission from mother to infant, after liver transplantation, on immunosuppressive therapy and during HCV treatment.

Recommendations for the treatment of hepatitis C in 2017.

The goals of treatment is to eliminate HCV infection, stop or reverse histological changes, reduce the risk of hepatocellular carcinoma development and transmission of the infection to other individuals. According to the recommendation of the Polish Group of Experts for HCV in 2017 all patients with chronic HCV infection should receive treatment, but it is not recommended in patients at high risk of short overall survival. If access to therapy is restricted, priority should be given to patients whose HCV infection can lead to an unfavourable outcome of the disease within a short time frame, particular to individuals with liver cirrhosis, rapidly progressing liver fibrosis, extrahepatic manifestations of HCV infection, chronic kidney diseases, patients before and after organ transplantation. Current recommendations of Polish Group of Experts for HCV provide guidelines to select optimal medication, assessment of liver fibrosis, treatment efficacy, dealing with resistance to direct acting antivirals, monitoring for hepatocellular carcinoma, management of HBV/HCV coinfection and drug interactions. It constains also advice on treatment of special patients populations such as renal failure, liver transplant and hepatic decompensation, as well as retreatment of patients which failed interferon free therapy. Moreover specific recommendations of management patients infected with different genotypes with currently reimbursed regimens or those expected to become available shortly in Poland are also included.

Forecasting the disease burden of chronic hepatitis C virus in Poland.

BACKGROUND AND AIMS: Chronic hepatitis C virus infection is prevalent among 200,000 individuals in Poland; however, few are aware of their condition (30,000 diagnosed) and even fewer are treated (2490 in 2014). This analysis projected future disease burden and developed two treatment scenarios to control or eliminate hepatitis C virus-related disease in Poland. METHODS: Using a modeling approach, the infected population and future disease progression were quantified. Baseline variables included viremic prevalence, age and sex, diagnosis rate, treatment rate, disease progression, and sustained virologic response rates. Data were collected from the literature and through expert interviews. RESULTS: The number of prevalent hepatitis C virus infections is projected to decrease (5%) by 2030. However, the numbers of individuals with compensated and decompensated cirrhosis, and hepatocellular carcinoma are estimated to increase by 40, 55, and 60%, respectively. By increasing sustained virologic response rates to 95% from 2015 onward, and the number of treated cases (from 2490 to 5000), the number of individuals with cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma is projected to remain constant until 2030. A strategy to eliminate chronic hepatitis C virus infection was also considered. To reduce total infections by 90% and mortality by 80%, treatment was increased to 15,000 patients annually. This scenario required the diagnosis of 15,000 new cases (compared with 3000 today). CONCLUSION: A marked reduction in hepatitis C virus-related disease burden is possible, with increased diagnosis and treatment. The results could inform the development of effective disease management in Poland.

Efficacy of pegylated interferon α-2b and ribavirin in chronic hepatitis C virus (genotypes 1 and 4) infection.

BACKGROUND AND OBJECTIVE: The course of chronic hepatitis C in children is often mild or asymptomatic, but may lead to liver cirrhosis and neoplasm. The aim of our study was retrospective evaluation of treatment efficacy using pegylated interferon (IFN)-α2b with ribavirin in children and adolescents with chronic hepatitis C, both treatment naïve and re-treated. METHODS: The study comprised 79 patients with chronic hepatitis C ages 8 to 18 years (43 patients re-treated; 54 infected with genotype 1 hepatitis C virus and 25 with genotype 4), treated with pegylated IFN-α2b (1.5 µg · kg⁻¹ · week⁻¹) plus ribavirin (15 mg · kg⁻¹ · day⁻¹) for 48 weeks. The primary endpoint was sustained virologic response (SVR). RESULTS: Early viral response (EVR) was observed in 43.1% and end-of-treatment response in 47.9% of patients. In 44.3% of patients, SVR was achieved, which was maintained for at least the next 6 months. Patients not treated before significantly more frequently attained EVR, end-of-treatment response, and SVR (64%, 65.6%, and 63.9%, respectively) as compared with re-treated patients (30%, 33.3%, and 27.9%, respectively). Among 28 patients who attained EVR, 23 achieved SVR. In 2 patients, despite lack of EVR, SVR was observed. There were numerous adverse effects. They were not so severe as to discontinue therapy. CONCLUSIONS: Combined therapy with pegylated IFN-α2b and ribavirin in patients with chronic hepatitis C, infected with hepatitis C virus genotypes 1 and 4, was more effective in treatment-naïve patients (63.9%) as compared with re-therapy cases (27.9%). SVR was maintained for at least the next 6 months in all of the patients. The applied treatment has limited efficacy and evokes numerous adverse effects; thus, search for new methods of treatment is mandatory.

Vertical genotype 1 HCV infection treated successfully in the second year of life: a case report.

BACKGROUND: Perinatal HCV transmission appears to be an important cause of HCV in children. Treatment of chronic hepatitis C in young children is controversial because of spontaneous HCV clearance and possible adverse events. CASE REPORT: Vertical HCV genotype 1 infection was diagnosed in a 3-month-old infant. In the subsequent clinical examination we still observed hepatomegaly, fluctuations of ALT, AST and GGT activity, with the highest values 2206 U/L, 1319 U/L, and 297 U/L, respectively. In qPCR, HCV RNA was >700.000 IU/ml. In the 42nd week of observation, liver biopsy was performed with Grade 1 grading and Grade 1 staging. At age 12 months, interferon-alpha2b (1.5 MU 3 times a week) and ribavirin (2×80 mg daily) were administered for 48 weeks. At the beginning of the treatment we observed fever after IFN injection. In the 12th week of therapy, HCV RNA disappeared followed by SVR, and it was sustained for 6 years. To our knowledge, this is the first report of a pediatric (1-year-old) patient treated with combined IFN alpha-2b and ribavirin therapy. CONCLUSIONS: This case report confirms the possibility of successful anti-HCV treatment in a young child, with 6-year sustained virological response without significant adverse events.

[Long-term therapy with nucleoside analog entecavir (baraclude) in patients with chronic hepatitis B]. / Dlugoterminowe leczenie pacjentów z przewleklym zapaleniem watroby typu B analogiem nukleozydowym entekawirem (baraclude).

Complications of HBV infection include cirrhosis and hepatocellular carcinoma (HCC), which together cause over 500.000 deaths annually. There are many risk factors of disease progression as: age, sex, comorbidities, family history, HBV genotypes, viral load, HBeAg status, disease stage etc. Chronic hepatitis B patients with high viral load have the highest risk of progressing to these life-threatening complications. The management of chronic hepatitis B currently rests with long-term therapy using nucleoside analogs. The goal of this therapy is sustained HBV DNA suppression, improving quality of life and preventing progression of the disease to cirrhosis, end-stage liver disease, HCC and death. The major limitations of long-term therapy is antiviral resistance. Entecavir provides sustained viral suppression and histological benefit with minimal resistance during long-term treatment of chronic hepatitis B, it is well-tolerable and has good safety profile, simple dosing and simple monitoring requirements.

Circulating endothelial cells in coronary artery disease.

BACKGROUND: endothelial damage and dysfunction play a crucial role in the pathophysiology of coronary artery disease (CAD). The quantification of circulating endothelial cells (CEC) in the peripheral blood is a novel method for assessing endothelial damage. AIM: to evaluate the possible diagnostic use of single quantification of CEC in peripheral blood by flow cytometry in patients with CAD. METHODS: we examined 48 patients with CAD, including 23 patients with acute myocardial infarction (AMI) and 25 patients with stable angina (SA). The control group consisted of 20 healthy subjects without symptoms of CAD. The CEC count was evaluated by flow cytometry using antibodies against CD31, CD146, and CD45. Plasma biochemical markers of endothelial damage (von Willebrand Factor [vWF], thrombomodulin [TM]) were measured by ELISA. Serum concentrations of troponin I (TnI) and lipid parameters were also included in the statistical analysis. RESULTS: A significant increase in the CEC count was found in patients with AMI compared to the control group (p < 0.05) and SA patients (p < 0.05). However, no difference was found in the CEC count between patients with SA and the control group. Increased vWF activity was found in both groups of CAD patients compared to the control group (AMI: p < 0.001, SA: p , 0.01), and vWF activity was significantly higher in AMI patients compared to SA patients (p < 0.001). Thrombomodulin concentration did not differ significantly between any patient groups and the control group. The CEC count correlated positively with vWF activity (r = 0.3852, p < 0.05) and the atherogenic index TC/HDL-C (r = 0.3844, p < 0.05) in all patients with CAD (AMI + SA). The sensitivity of CEC count for the diagnosis of an acute coronary syndrome was lower than that of TnI level on admission (39% vs 69%). CONCLUSIONS: we confirmed that CEC count in peripheral blood can be determined by flow cytometry in CAD patients with both AMI and SA. The CEC count in AMI was increased in comparison to healthy subjects and SA patients in one third of all cases. To determine whether CEC count could be used to improve the diagnosis of an acute coronary syndrome in patients with CAD, additional studies in larger patient groups would be required.

Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B.

UNLABELLED: One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) resulted in significantly improved liver histology and virological and biochemical endpoints in comparison with lamivudine. Patients who received at least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term rollover study and underwent long-term liver biopsy were evaluated for improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive and 19 HBeAg-negative] receiving entecavir therapy underwent long-term liver biopsy (median time of biopsy = 6 years, range = 3-7 years). Histological improvement was analyzed for 57 patients who had adequate baseline biopsy samples, baseline Knodell necroinflammatory scores > or =2, and adequate long-term biopsy samples. At the time of long-term biopsy, all patients in the cohort had a hepatitis B virus DNA level <300 copies/mL, and 86% had a normalized alanine aminotransferase level. Histological improvement (> or =2-point decrease in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis score) was observed in 96% of patients, and a > or =1-point improvement in the Ishak fibrosis score was found in 88% of patients, including all 10 patients with advanced fibrosis or cirrhosis at the phase 3 baseline. CONCLUSION: The majority of nucleoside-naive patients with CHB who were treated with entecavir in this long-term cohort achieved substantial histological improvement and regression of fibrosis or cirrhosis.

[HBV and HCV coinfections in children--own investigations]. / Zakazenia mieszane HBV i HCV u dzieci z uwzglednieniem badan wlasnych.

Problem of HBV and HCV coinfection is controversial. HCV superinfection seems to be the co-factor of HBV infection, so as factor inhibiting HBV replication. According to some authors in HBV, HCV co-infection more advanced morphological liver changes and progression to hepatocellular carcinoma were observed. It concerns so patients with active as an "occult" hepatitis B. In this work the results of our own investigations were presented in which beneficial influence of HCV superinfection on chronic B hepatitis in children was revealed. Our study confirmed opinions of both viruses interference.

Selenium, glutathione and glutathione peroxidases in blood of patients with chronic liver diseases.

Disturbances in the antioxidant system could play a role in pathogenesis of chronic liver disease. The aim of our study was to evaluate the levels/activities of antioxidants in blood of patients with chronic liver disease. We estimated selenium and glutathione concentrations and glutathione peroxidase activities in blood of 59 patients with chronic hepatitis B or C virus infection (group 1) and 64 patients with alcoholic, autoimmune or cryptogenic chronic liver disease (group 2). The results were compared with 50 healthy controls. Whole blood and plasma selenium and red cell glutathione concentrations were significantly lower in the patients compared with the controls. Red cell glutathione peroxidase activity was slightly reduced in both subgroups of group 1 and in group 2 with normal alanine aminotransferase values. Plasma glutathione peroxidase activity was slightly but significantly higher in patients with elevated aminotransferase values. The findings suggest that disturbances in antioxidant parameters in blood of patients with chronic liver disease may be the cause of the peroxidative damage of cells.

Supplementation with antioxidant vitamins prevents oxidative modification of DNA in lymphocytes of HIV-infected patients.

There is evidence suggesting that patients infected with human immunodeficiency virus (HIV) are under chronic oxidative stress. In the present study, the level of oxidatively modified bases in lymphocyte DNA and some other parameters of oxidative stress were measured in HIV-infected patients (n = 30), as well as in control groups (10 healthy volunteers and 15 HIV-seronegative injected drug users). Additional experiments were conducted using lymphocyte DNA samples from asymptomatic seropositive, HIV-infected patients who were supplemented with antioxidant vitamins A, C, and E or received placebo. Significant increases in the amount of the modified DNA bases were observed in HIV-infected patients when compared with the control group. The concentration of thiobarbituric acid reactive substances (TBARS) was higher and activities of antioxidant enzymes (superoxide dismutase and catalase) were lower in the group of HIV-infected patients in comparison to the control group. Vitamin supplementation resulted in the significant decrease in the levels of all modified DNA bases when compared to the patients who received placebo. The reduction of TBARS and the restoration of the activity of the enzymes were also observed. Our data suggest that people infected with HIV can benefit from treatment with antioxidant vitamins.