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The relationship between left ventricle (LV), extracellular matrix remodeling and fibrosis-linked amphiregulin (ARG) in cirrhotic cardiomyopathy (CCM) is unknown. The aim of the study was to investigate the associations between markers of extracellular matrix remodeling and ARG in cirrhosis and their association with indicators of ventricular remodeling and LV functional parameters. In hepatitis C virus (HCV) patients with cirrhosis, who underwent echocardiography, the presence of left ventricular diastolic dysfunction (LVDD) was determined by having gradable diastolic dysfunction in accordance with modified 2020 Cirrhotic Cardiomyopathy Consortium criteria. A total of 87 cirrhotic patients were consecutively analyzed. Based on detailed echocardiographic assessment - 35 HCV patients with cirrhosis had normal left ventricular diastolic function (non-CCM group), whereas 52 patients had LVDD (CCM group). ARG was measured by enzyme-linked immunosorbent assay. The ARG levels were significantly increased in the CCM group compared to the non-CCM group (P<0.001). ARG levels in all HCV patients were independently associated to the presence of CCM, and showed significant correlations with LVDD. The close relationship between ARG levels and the direct serum marker of fibrosis, and selected markers of extracellular matrix (i.e. transforming growth factor-beta1 (TGF-β1), and carboxyterminal propeptide of type I collagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), tissue inhibitor of matrix proteinase-1 (TIMP-1), respectively), ventricular remodeling (i.e. N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-T (hs-TnT)), and LV functional parameters suggest an active role in the myocardial injury. Using ROC analysis, the best marker for the diagnosis of CCM was NT-proBNP with AUROC = 0.796. The area under the curve of ARG (AUROC = 0.709) for predicting CCM was greater than this for PICP (AUROC = 0.662) and similar to this hs-TnT (AUROC = 0.753). The simultaneous monitoring of serum ARG and markers of extracellular matrix and ventricular remodeling can be helpful for the alterations in myocardial function control in HCV patients with cirrhosis. [ABSTRACT FROM AUTHOR]

The presence of type 2 diabetes mellitus (DM) in patients with cirrhosis is associated with an increased risk of spontaneous bacterial peritonitis (SBP) which may represent an increased susceptibility to infections. Endocan is a key player in the regulation of inflammatory disorders, and a biomarker in bacteremia and sepsis. To investigate the association between both endocan and DM, and developing SBP, we conducted a retrospective cohort study. Three hundred and thirty patients (179 men, 151 women; mean age 61.0 ± 8.5 years) who were treated for liver cirrhosis were studied between January 2007 and December 2016. Univariate and multivariate analyses using age, type 2 diabetes mellitus, severity of cirrhosis (Child-Pugh or MELD score), platelet count, serum proinflammatory cytokines, procalcitonin, C-reactive protein, and endocan level were conducted to identify factors related to the development of SBP. Among 330 patients with the median follow-up of 6.0 years, the cumulative incidence of SBP at 5 years was 28.6%. On multivariate analysis, a high serum endocan level and DM were independent and significant risk factors for SBP development (hazard ratio (HR) 1.634 (95% CI: 1.012 - 2.638; P = 0.047) and 2.482 (95% CI: 1.134 - 5.412; P = 0.023), respectively). Furthermore, the cumulative incidence rate of SBP in cirrhotic patients with high endocan levels was significantly greater than that in patients with low endocan levels (P = 0.035; log-rank test). Endocan is an independent predictor of SBP development in patients with cirrhosis. Cirrhotic patients with type 2 diabetes mellitus who have a higher endocan levels should be monitored carefully for the development of spontaneous bacterial peritonitis. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy with immune checkpoint inhibitors combined with an anti-angiogenic tyrosine-kinase inhibitor (TKI) has been shown to improve overall survival versus anti-angiogenic therapy alone in advanced solid tumours, but not in hepatocellular carcinoma. Therefore, a clinical study was conducted to compare the efficacy and safety of the anti-PD-1 antibody camrelizumab plus the VEGFR2-targeted TKI rivoceranib (also known as apatinib) versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma., Methods: This randomised, open-label, international phase 3 trial (CARES-310) was done at 95 study sites across 13 countries and regions worldwide. Patients with unresectable or metastatic hepatocellular carcinoma who had not previously received any systemic treatment were randomly assigned (1:1) to receive either camrelizumab 200 mg intravenously every 2 weeks plus rivoceranib 250 mg orally once daily or sorafenib 400 mg orally twice daily. Randomisation was done via a centralised interactive response system. The primary endpoints were progression-free survival, as assessed by the blinded independent review committee per Response Evaluation Criteria in Solid Tumours version 1.1, and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drugs. We report the findings from the prespecified primary analysis for progression-free survival and interim analysis for overall survival. This study is registered with ClinicalTrials.gov (NCT03764293)., Findings: Between June 28, 2019, and March 24, 2021, 543 patients were randomly assigned to the camrelizumab-rivoceranib (n=272) or sorafenib (n=271) group. At the primary analysis for progression-free survival (May 10, 2021), median follow-up was 7·8 months (IQR 4·1-10·6). Median progression-free survival was significantly improved with camrelizumab-rivoceranib versus sorafenib (5·6 months [95% CI 5·5-6·3] vs 3·7 months [2·8-3·7]; hazard ratio [HR] 0·52 [95% CI 0·41-0·65]; one-sided p<0·0001). At the interim analysis for overall survival (Feb 8, 2022), median follow-up was 14·5 months (IQR 9·1-18·7). Median overall survival was significantly extended with camrelizumab-rivoceranib versus sorafenib (22·1 months [95% CI 19·1-27·2] vs 15·2 months [13·0-18·5]; HR 0·62 [95% CI 0·49-0·80]; one-sided p<0·0001). The most common grade 3 or 4 treatment-related adverse events were hypertension (102 [38%] of 272 patients in the camrelizumab-rivoceranib group vs 40 [15%] of 269 patients in the sorafenib group), palmar-plantar erythrodysaesthesia syndrome (33 [12%] vs 41 [15%]), increased aspartate aminotransferase (45 [17%] vs 14 [5%]), and increased alanine aminotransferase (35 [13%] vs eight [3%]). Treatment-related serious adverse events were reported in 66 (24%) patients in the camrelizumab-rivoceranib group and 16 (6%) in the sorafenib group. Treatment-related death occurred in two patients: one patient in the camrelizumab-rivoceranib group (ie, multiple organ dysfunction syndrome) and one patient in the sorafenib group (ie, respiratory failure and circulatory collapse)., Interpretation: Camrelizumab plus rivoceranib showed a statistically significant and clinically meaningful benefit in progression-free survival and overall survival compared with sorafenib for patients with unresectable hepatocellular carcinoma, presenting as a new and effective first-line treatment option for this population., Funding: Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics., Competing Interests: Declaration of interests SLC reports honoraria from AstraZeneca, Eisai, Merck Sharp & Dohme, Roche, and Bayer; consulting or advisory roles for AstraZeneca, Eisai, Merck Sharp & Dohme, Bristol Myers Squibb, and Roche; and research funding from Eisai and Ipsen. A-LC reports consulting or advisory roles for Merck Sharp & Dohme, Bristol Myers Squibb, Bayer Healthcare, AstraZeneca, Genentech/Roche, IPSEN Innovation, BeiGene, and EXE; speaker's bureau for Ono Pharmaceutical, Bayer Yakuhin, Novartis, Amgen Taiwan, and Chugai Pharmaceutical; expert testimony for Merck Sharp & Dohme, Ono Pharmaceutical, Eisai, and IPSEN Innovation; and participation on an advisory board for Abbisko Therapeutics. AV reports personal fees from AstraZeneca, Amgen, BeiGene, Böhringer Mannheim, Bristol Myers Squibb, BTG, Daiichi Sankyo, Eisai, Incyte, Ipsen, Merck Sharp & Dohme, PierreFabre, Roche, Servier, Sirtex, Tahio, Terumo, Jiangsu Hengrui Pharmaceuticals, GSK, and Imaging Equipment (Advanced Accelerator Applications). XLia, CC, and LW were employees of Jiangsu Hengrui Pharmaceuticals at the time of the study. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: In Poland, active HCV infection affects between 0.4 and 0.5% of the population, i.e., about 150,000 people, while the number of patients with epilepsy is estimated to be 350,000-400,000. Currently available antiviral therapies show little interaction with neurological drugs. The aim of our study was to evaluate the effectiveness and safety of the treatment of chronic HCV infection in patients with coexisting epilepsy., Methods: A total of 184 epilepsy patients were selected from the group of 10,152 HCV-infected patients treated for HCV infection within the Epiter-2 database from 2015 to 2018. Comparing the effectiveness and safety of anti-HCV regimens between the patients with comorbid epilepsy and 3573 patients without comorbidities was our study's objective., Results: The effectiveness of anti-HCV treatment was high in both the sample and the control group. No statistically significant SVR difference was observed between the sample group, with ITT = 93.5% and mITT = 95.5%, and the control group, with ITT = 95.2% and mITT = 97.5%, regardless of the genotype and the stage of liver disease at the start of therapy. The treatment was safe in patients with epilepsy., Conclusions: The effectiveness and safety of HCV treatment in patients with epilepsy are comparable to those of patients with no significant comorbidities.

Background: About 20% of patients infected with SARS-CoV-2 develop COVID-19-the disease that has dominated health care in the last two years. The course of COVID-19 in patients with advanced liver disease tends to be severe, patients also suffer from a higher risk of complications and death. The primary object of this study was to assess the risk and causes of death in patients with cirrhosis and hepatocellular carcinoma (HCC)., Materials and Methods: From a group of 4,314 patients hospitalized at Jerzy Gromkowski Regional Specialist Hospital in Wroclaw (Poland) due to SARS-CoV-2/COVID-19 infection between March 15, 2020, and January 31, 2022, we selected a cohort of 31 patients with liver cirrhosis (12 women and 19 men) and 7 patients with HCC developed on the cirrhotic liver (1 woman, 6 men). The control group included 123 patients without liver disease. In the entire cohort, we analyzed the course of COVID-19 infection, baseline oxygen demand, liver function (assessed using the CTP-Child-Turoctte-Pugh score and MELD-Model of End-Stage Liver Disease scales), length of hospitalization, development of acute-on-chronic liver failure, and deaths., Results: The mean age of the patients was 56.6 years in the liver cirrhosis group, 63.3 years for patients with (HCC) hepatocellular carcinoma, and 64 years in the control group. Time of hospitalization averaged 15.52 days and 11.14 days for patients with liver cirrhosis and liver cancer, respectively. For the control group, the average duration of the hospital stay was 11.61 days. With respect to baseline liver function assessed using the CTP score, in the cirrhosis group 10 patients were CTP class A, 19 patients were class B and 9 patients were class C. The cancer group included 3 patients with class A, 2 patients with class B, and 2 patients with class C. In the studied cohort, 22 patients had a baseline MELD score < 12 points, and in 15 patients was > 12. In the HCC group, it was, respectively, CTP A:3, B: 2, C: 2, and MELD < 12: 3, ≥12: 4 people. Most of these patients presented with a progression of liver disease. Fifteen patients died, including 12 with cirrhosis and 3 with HCC, accounting for 39.47% in the entire cohort, 39% in the cirrhotic group and 43% in the HCC group, and 13 in the control group (10.6%), There was a clear statistical difference between the mortality rate in the group with liver disease and in the control group., Conclusions: Infection with SARS-CoV-2/COVID-19 in patients with cirrhosis and HCC tends to have a more severe course and leads to exacerbation of the liver disease. The most common cause of death in the analyzed cohort infected with SARS-CoV-2/COVID-19 was the progression of liver disease, complicated by liver failure., (© 2022. The Author(s).)

The emergence of a highly transmissible and a more pathogenic B.1.617.2 (delta) variant of SARS-CoV-2 has brought concern over COVID-19 vaccine efficacy and the increased risk of severe breakthrough infections. The objective of this study was to assess the frequency and the clinical characteristics of severe breakthrough COVID-19 cases recorded in 10 Polish healthcare units between 1 June and 31 December 2021, a period during which a rapid surge in the share of B.1.617.2 infections was seen, while a significant number of populations were already fully vaccinated. Overall, 723 individuals who completed the initial vaccination regime (fully vaccinated group) and an additional 18 who received a booster dose were identified—together, they represented 20.8% of all the COVID-19 patients hospitalized during the same period in the same healthcare institutions (0.5% in the case of a group that received a booster dose). Although laboratory and clinical parameters did not differ between both groups, patients who received a booster tended to have lower CRP, IL-6, PCT, and d-dimer levels and they required oxygen therapy less frequently. The most common early COVID-19 symptoms in the studied group were fatigue, cough, fever (>38 °C), and dyspnea. Individuals with no detectable anti-spike IgG antibodies constituted 13%; the odds of being a humoral non-responder to the vaccine were increased in patients aged >70 years. Fully vaccinated patients hospitalized after more than 180 days from the last vaccine dose were significantly older and they were predominantly represented by individuals over 70 years and with comorbidities, particularly cardiovascular disease. Contrary to mRNA vaccines, most patients vaccinated with adenoviral vector vaccines were infected within six months. A total of 102 fatal cases (14% of all deaths among vaccinated individuals; 0.7% in the case of a group that received a booster dose) were recorded, representing 17.6% of all the COVID-19 fatalities recorded in June−December 2021 in the considered healthcare units. The odds of death were significantly increased in men, individuals aged >70 years, patients with comorbidities, and those identified as humoral non-responders to vaccination; in fully vaccinated patients the odds were also increased when the second vaccine dose was given >180 days before the first COVID-19 symptoms. The mortality rate in immunocompromised subjects was 19%. The results indicate that compared to vaccinated individuals, severe COVID-19 and deaths in the unvaccinated group were significantly more prevalent during the B.1.617.2-dominated wave in Poland; and, it highlight the protective role of a booster dose, particularly for more vulnerable individuals.

Advanced hepatocellular carcinoma (HCC) is an aggressive disease associated with poor prognosis. Tumor Treating Fields (TTFields) therapy is a non-invasive, loco-regional treatment approved for glioblastoma and malignant pleural mesothelioma. HCC preclinical and abdominal simulation data, together with clinical results in other solid tumors, provide a rationale for investigating TTFields with sorafenib in this patient population. HEPANOVA was a phase II, single arm, historical control study in adults with advanced HCC (NCT03606590). Patients received TTFields (150 kHz) for ≥18 h/day concomitant with sorafenib (400 mg BID). Imaging assessments occurred every 12 weeks until disease progression. The primary endpoint was the overall response rate (ORR). Safety was also evaluated. Patients (n = 27 enrolled; n = 21 evaluable) had a poor prognosis; >50% were Child−Turcotte−Pugh class B and >20% had a baseline Eastern Clinical Oncology Group performance status (ECOG PS) of 2. The ORR was higher, but not statistically significant, for TTFields/sorafenib vs. historical controls: 9.5% vs. 4.5% (p = 0.24), respectively; all responses were partial. Among patients (n = 11) with ≥12 weeks of TTFields/sorafenib, ORR was 18%. Common adverse events (AEs) were diarrhea (n = 15/27, 56%) and asthenia (n = 11/27, 40%). Overall, 19/27 (70%) patients had TTFields-related skin AEs; none were serious. TTFields/sorafenib improved response rates vs. historical controls in patients with advanced HCC, with no new safety concerns or related systemic toxicity.

SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and-where it is particularly challenging-on vascular endothelial cells. Liver involvement is a rare manifestation of COVID-19., Material and Methods: We reviewed 450 patients admitted due to the fact of SARS-CoV-2 infection (COVID-19) including 88 with liver injury. Based on medical history and previous laboratory test results, we excluded cases of underlying liver disease. The analysis involved a clinical course of COVID-19 in patients without underlying liver disease as well as the type and course of liver injury., Results: Signs and symptoms of liver injury were present in 20% of patients, mostly presenting as a mixed-type pattern of injury with less common cases of standalone hepatocellular (parenchymal) or cholestatic injury. The liver injury symptoms resolved at the end of inpatient treatment in 20% of cases. Sixteen patients died with no cases where liver injury would be deemed a cause of death., Conclusions: (1) Liver injury secondary to COVID-19 was mild, and in in 20%, the signs and symptoms of liver injury resolved by the end of hospitalization. (2) It seems that liver injury in patients with COVID-19 was not associated with a higher risk of mortality. (3) The underlying mechanism of liver injury as well as its sequelae are not fully known. Therefore, caution and further monitoring are advised, especially in patients whose liver function tests have not returned to normal values.

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a major health burden worldwide due to high mortality rates and hospital bed shortages. SARS-CoV-2 infection is associated with several laboratory abnormalities. We aimed to develop and validate a risk score based on simple demographic and laboratory data that could be used on admission in patients with SARS-CoV-2 infection to predict in-hospital mortality., Methods: Three cohorts of patients from different hospitals were studied consecutively (developing, validation, and prospective cohorts). The following demographic and laboratory data were obtained from medical records: sex, age, hemoglobin, mean corpuscular volume (MCV), platelets, leukocytes, sodium, potassium, creatinine, and C-reactive protein (CRP). For each variable, classification and regression tree analysis were used to establish the cut-off point(s) associated with in-hospital mortality outcome based on data from developing cohort and before they were used for analysis in the validation and prospective cohort. The covid-19 score was calculated as a sum of cut-off points associated with mortality outcome., Results: The developing, validation, and prospective cohorts included 129, 239, and 497 patients, respectively (median age, 71, 67, and 70 years, respectively). The following cut of points associated with in-hospital mortality: age > 56 years, male sex, hemoglobin < 10.55 g/dL, MCV > 92.9 fL, leukocyte count > 9.635 or < 2.64 10 3 /µL, platelet count, < 81.49 or > 315.5 10 3 /µL, CRP > 51.14 mg/dL, creatinine > 1.115 mg/dL, sodium < 134.7 or > 145.4 mEq/L, and potassium < 3.65 or > 6.255 mEq/L. The AUC of the covid-19 score for predicting in-hospital mortality was 0.89 (0.84-0.95), 0.850 (0.75-0.88), and 0.773 (0.731-0.816) in the developing, validation, and prospective cohorts, respectively (P < 0.001The mortality of the prospective cohort stratified on the basis of the covid-19 score was as follows: 0-2 points,4.2%; 3 points, 15%; 4 points, 29%; 5 points, 38.2%; 6 and more points, 60%., Conclusion: The covid-19 score based on simple demographic and laboratory parameters may become an easy-to-use, widely accessible, and objective tool for predicting mortality in hospitalized patients with SARS-CoV-2 infection., (© 2021. The Author(s).)

Background and Aims: The aim of this study was to assess the real-life effectiveness and safety of direct acting antivirals (DAAs) in patients with cirrhosis and history of hepatic decompensation compared to those with compensated cirrhosis., Method: Data of patients treated with DAAs and included in the EpiTer-2 database (N = 10 152) were collected retrospectively. The primary endpoint was sustained viral response (SVR) at 12 weeks posttreatment. Patients were also evaluated in terms of liver-related adverse events and treatment modification/discontinuation., Results: The overall SVR rate was 91.4% in the intent to treat (ITT) analysis and 95.2% in the per-protocol (PP) analysis (P < .001). Patients with decompensated cirrhosis had lower SVR rates compared to those with compensated cirrhosis in ITT analysis (86.4% vs 92.0%, P < .001), while not in PP analysis (92.9% vs 95.5%, P > .05). Adverse events (AE) occurred 45.6% and 29.3% of patients with decompensated and compensated cirrhosis (P < .001). Patients with decompensated cirrhosis were at higher risk of death (5.4% vs 0.9%; P < .0001) or liver decompensation (21.5% vs 1.3%; P < .0001). Treatment with protease inhibitors was not associated with hepatic decompensation (P = .3). Only 82.6% of patients with decompensated cirrhosis completed DAA treatment (vs 92.8% in compensated cirrhotics; P < .0001)., Conclusion: Despite higher frequency of AE and treatment modifications, once completed, DAAs yield comparable results for patients with decompensated and compensated cirrhosis. High rate of serious adverse events in patients with advanced liver disease treated with PI may not be related to the detrimental effect of the medications, but rather to the disease itself., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

(1) Background: Treatment of hepatitis C virus (HCV) infections with direct-acting antivirals (DAA) has demonstrated high efficacy and an excellent safety profile. The cured patients showed a sustained virological response and improved liver function, but also a continued risk of hepatocellular carcinoma (HCC) during the 2-3 years of follow-up after treatment; (2) Methods: A total of 192 patients out of 209 of the primary AMBER study were analyzed five years after treatment with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin. Results: We confirmed that HCV clearance after DAA treatment is stable regardless of baseline liver fibrosis. We found that sustained virologic response is associated with a gradual but significant reduction in liver stiffness over 5 years. Liver function improved during the first 2 years of follow-up and remained stable thereafter. The risk of death due to HCC as well as death due to HCV persists through 5 years of follow-up after successful DAA treatment. However, in non-cirrhotic patients, it appears to clear up 3 years after treatment; (3) Conclusions: Monitoring for more than 5 years after curing HCV infection is necessary to assess the long-term risk of possible development of HCC, especially in patients with cirrhosis of the liver.

The clinical trials of the COVID-19 vaccines that are authorized in the European Union have revealed high efficacy in preventing symptomatic infections. However, during vaccination campaigns, some vaccine recipients, including those partially and fully vaccinated, will experience severe COVID-19, requiring hospitalization. This may particularly concern patients with a diminished immune response to the vaccine, as well as non-responders. This work has retrospectively analyzed the 92 cases of patients who were hospitalized between 27 December 2020 and 31 May 2021 in four Polish healthcare units due to COVID-19, and who have previously received the COVID-19 vaccine (54.3% ≤ 14 days after the first dose, 26.1% > 14 days after the first dose, 7.6% ≤ 14 days after the second dose, and 12% > 14 days after the second dose). These patients represented a minute fraction (1.2%) of all the COVID-19 patients who were hospitalized during the same period in the same healthcare institutions. No significant differences in white blood count, absolute lymphocyte count nadir, C-reactive protein, interleukin-6, procalcitonin, oxygen saturation, lung involvement, and fever frequency were found between the recipients of the first and second vaccine dose. A total of 15 deaths were noted (1.1% of all fatal COVID-19 cases in the considered period and healthcare units), including six in patients who received the second dose (five > 14 days after the second dose)-three of these subjects were using immunosuppressive medicines, and two were confirmed to be vaccine non-responders. The study reassures that severe COVID-19 and deaths are not common in vaccinated individuals, highlights that the clinical course in such patients may not reveal any distinctive features, and advocates for close monitoring of those at a higher risk of vaccine failure.

Aim of the Study: Hepatotropic viruses cause metabolic disturbances such as insulin resistance and hepatosteatosis. Moreover, metabolic factors, such as insulin resistance, obesity, and type 2 diabetes mellitus, increase the risk for hepatocellular carcinoma (HCC) in patients with virus-related liver cirrhosis. Cytokines secreted by the adipose tissue (adipokines) may be implicated in these metabolic disturbances, but there is little evidence regarding the role of adipokines in virus-related cirrhosis and HCC. Thus, we studied whether serum concentrations of selected adipokines were altered in patients with virus-related liver cirrhosis, including patients with HCC., Material and Methods: We included 43 patients with liver cirrhosis due to chronic hepatitis B or chronic hepatitis C. Of these patients, 36 had HCC and 7 did not have any malignant lesions. In addition to routine clinical and laboratory variables, we analyzed serum concentrations of betatrophin, insulin, vaspin, visfatin, and irisin., Results: Compared with healthy controls, patients with HCC had significantly increased vaspin concentrations and significantly reduced irisin concentrations. Compared with controls, patients with virus-related cirrhosis, with or without HCC, had significantly increased concentrations of insulin and betatrophin. The serum visfatin concentration was non-significantly higher in patients with virus-related cirrhosis than in controls. None of the studied adipokines was a significant predictor of HCC. Serum concentrations of the studied adipokines were not related to cirrhosis severity or HCC stage., Conclusions: Metabolic parameters, including serum adipokine concentrations, are altered in patients with virus-related liver cirrhosis. Adipokines might be related to the HCC risk in these patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Clinical and Experimental Hepatology.)

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS Coronaviridae infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.

Introduction: Noninvasive methods are increasingly used in the clinical assessment of patients with chronic hepatitis C (CHC)., Objectives: We aimed to develop a predictive model for the evaluation of significant fibrosis in patients with CHC, based on serum biomarkers. We compared the accuracy of our model in detecting significant fibrosis with currently known markers / models of fibrosis (such as the aspartate aminotransferase to platelet ratio index [APRI], the Fibrosis‑4 [FIB-4] score, and the Forns index)., Patients and Methods: A total of 242 patients with CHC not receiving antiviral treatment were divided into 2 groups: training group (n = 150) and validation group (n = 92). Significant fibrosis was defined as F2 or higher on the Meta‑analysis of Histological Data in Viral Hepatitis (METAVIR) scale., Results: Multivariable analysis revealed that age (P <0.001), pentraxin 3 (PTX3) levels (P = 0.009), γ‑glutamyl transpeptidase (GGT) to platelet count (PLT) ratio (P = 0.08), and hyaluronic acid levels (HA) (P = 0.07) were independent predictors of significant fibrosis. Based on that, we developed a model for predicting significant fibrosis: Pentra score = 0.176 × PTX3 (ng/ml) + 0.522 × HA (ng/ml) + 0.29 × GGT (IU/l) to PLT (×109/l) ratio + 0.14 × age (years) - 3.9346. Then, we compared our model with the biomarkers and models currently used to predict liver fibrosis. The Pentra score yielded the largest area under the receiver operating characteristic curve for predicting significant fibrosis in the training and validation groups (0.894 and 0.867, respectively). It also had the highest diagnostic accuracy in both groups (90.6% and 87.0%, respectively)., Conclusions: Our model for detecting significant fibrosis in patients with CHC using pentraxin 3 and other serum biomarkers compares well with the existing and previously published indices. However, further validation in larger cohorts is needed.

Hepatocellular carcinoma (HCC) development is a complex process with well-known risk factors, however the role of betatrophin/angiopoietin-like protein 8 and irisin has been poorly investigated thus far. The aim of this study is to measure betatrophin and irisin serum levels in HCC, cirrhotic patients and controls, assess their relationship with cancer etiology and grade, metabolic abnormalities and liver dysfunction severity. Serum betatrophin and irisin concentrations were measured with commercially available ELISA kits in 69 cirrhotic patients with HCC, 24 patients with non-viral cirrhosis and 20 healthy volunteers. The severity of liver disfunction was assessed according to Child-Pugh (C-P) score, while HCC grade according to the Barcelona clinic liver cancer (BCLC) staging system. Serum betatrophin concentration was significantly higher (33.7 ± 13.4 versus 12.3 ± 2.0 ng/ml; P < 0.001), while serum irisin level significantly lower in HCC patients compared to controls (2.52 ± 1.14 versus 4.46 ± 1.34 μg/ml; P = 0.02). Betatrophin level was also significantly elevated among cirrhotic patients compared to healthy volunteers. More evident serum betatrophin increase was found in patients with viral disease (34.8 ± 12.9 versus 26.1 ± 13.8 ng/ml; P < 0.001). Serum irisin concentration was significantly decreased in more advanced HCC cases (stage A versus C according to BCLC: 3.4 ± 1.3 versus 1.89 ± 1.1 μg/ml; P = 0.02). Decline of serum irisin (A: 3.4 ± 1.2; B: 2.42 ± 0.8; C: 1.91 ± 1.19 μg/ml; P = 0.03) and up-regulation of serum betatrophin levels (A: 24.1 ± 13.8; B: 39.3 ± 11.4; C: 46.2 ± 9.4 ng/ml; P = 0.03) were observed in patients with more advanced cirrhosis according to C-P score. We concluded that betatrophin serum level increased in cirrhotic patients, compared to controls. Since there was no difference between cirrhotic patients with and without intercurrent HCC, we suppose it may have an influence on fibrosis development, however not hepatocarcinogensis. Irisin serum level decreased in HCC patients, especially with more advanced disease grade, and was inversely related to the severity of liver disfunction.

Hepatocellular carcinoma (HCC) is the most common liver cancer, accountable for 90% cases. Visfatin and vaspin are adipocytokines with various suggested functions and proven significant correlations between BMI and percentage of body fat. The aim was to assess visfatin and vaspin serum levels in HCC patients and controls, compare their levels in patients with different cancer etiology and grade assessed according to the Barcelona-Clinic Liver Cancer (BCLC) staging system. The additional aim was to analyze relationship between analyzed adipokines and metabolic abnormalities and liver disfunction severity. The study was performed on 69 cirrhotic patients (54 males/15 females) with HCC, aged 59.0 ± 12.1 years, and with BMI 29.0 ± 4.5 kg/m2 compared to 20 healthy volunteers. Serum visfatin and vaspin concentrations were significantly increased in HCC patients compared to controls (p = 0.01 and p = 0.02, respectively). Serum vaspin was significantly higher in HCC patients with viral compared to those with non-viral etiology (p = 0.02), with more evident increase in chronic hepatitis C patients (CHC). Serum visfatin levels were significantly higher in patients with higher insulin resistance (p = 0.04) and with platelets count > 100 000/mm3 (p<0.001). Patients with BMI >30 kg/m2 had markedly up-regulated vaspin levels (p = 0.04). There was no difference in vaspin and visfatin serum levels with respect to liver dysfunction and BCLC classification. In conclusion, our study revealed serum vaspin and visfatin to be significantly increased in HCC patients independently of cancer etiology compared to controls. Additionally, serum vaspin was elevated in viral disease, especially in CHC. Vaspin up-regulation can be a compensatory mechanism against IR in HCC patients. Serum visfatin and vaspin, although up-regulated, seem not to be associated with cancer grade and cirrhosis severity., Competing Interests: The authors have declared that no competing interests exist.

Background: (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand., Methods: In this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients., Results: Of 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= -0.74, standard error [SE] = 0.16, P = 3.44 ×10-6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10-6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele., Conclusions: Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies., Clinical Trials Registation: NCT01401400., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Pentraxin 3 (PTX3) plays a pathogenic role in experimental models of chronic liver injury and contributes to the progression of fibrosis. The detection of advanced fibrosis (METAVIR F≥3) is important to identify patients who are in urgent need of antiviral treatments versus those whose treatment could be deferred (F≥2). The aim was to assess the diagnostic value of PTX3 as a potential biomarker for clinically significant and advanced fibrosis. PTX3 associations with biochemical and histological parameters of inflammatory activity and fibrosis were investigated in 138 patients with chronic viral hepatitis C (HCV) before antiviral treatment. METAVIR histological scores of activity and fibrosis were obtained. PTX3 was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of serum PTX3 levels was compared to that of other fibrosis markers, including transforming growth factor- β 1 (TGF- β 1 ), hyaluronic acid (HA), aspartate transaminase to platelet ratio index (APRI), fibrosis score based on four factors (FIB4), gamma-glutamyltranspeptidase to platelet ratio (GPR), and the liver stiffness measurement (LSM) by transient elastography (FibroScan®). In HCV patients the PTX3 level increased in parallel with the METAVIR histological score of activity, being independently associated with the METAVIR fibrosis score ( P < 0.001). Using the receiver operating characteristics analysis, the best marker for detecting F≥2 and F≥3 was PTX3 with AUC = 0.802 and AUC = 0.867, respectively. The area under the curve of PTX3 for predicting significant fibrosis (F≥2) was significantly greater than those for the GPR ratio (AUC = 0.648) and FIB-4 score (AUC = 0.770) and similar to that for APRI index (AUC = 0.831). PTX3 provided clinically relevant diagnostic accuracy as a single marker of significant fibrosis.

Background/aim: Type 2 diabetes mellitus (DM) frequently occurs in patients with chronic hepatitis C (CHC) and is associated with atherosclerosis, in which circulating microparticles (MPs) play an important role. We asked whether the presence of DM affects endothelial-derived (EMPs) and platelet-derived microparticles (PMPs) levels; and whether MPs levels associate with biomarkers of inflammation and oxidative stress in patients with CHC., Materials and Methods: Overall, 136 patients were enrolled in the study, 86 CHC patients (41 with DM with moderate glycemic control), 20 outpatients with DM and 30 controls. Circulating MPs were phenotyped by flow cytometry., Results: When the MPs levels were analyzed individually in CHC patients, there was a positive association of plasma apoptotic MPs with oxidative stress markers. We report a hitherto undescribed relationship between diabetes prevalence and apoptotic MPs-associated inflammation in patients with CHC., Conclusion: The presence of apoptotic MPs in the plasma of CHC patients, with increased levels being found in patients with DM and moderate glycemic control was herein demonstrated. The simultaneous monitoring of plasma apoptotic MPs, oxidative stress markers and inflammatory biomarkers can be helpful for the cardiovascular disease control in diabetic patients with CHC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Endoscopy methods involve diagnostics as well as therapy. Endoscopic techniques have a small but definite incidence of complication, so endoscopy should not be performed routinely but only on the basis of indication. The typical endoscopic procedures used in diagnostics and therapy of liver cirrhosis are endoscopy of upper and lower gastrointestinal tract. Other techniques are less common. Significance of endoscopy procedures increases in case of chronic progressive liver diseases, independently of etiology, where changes in gastrointestinal tract are observed in 87% of patients.

Life expectancy of patients with liver cirrhosis is closely linked to the degree of liver dysfunction and the occurrence of bacterial infection. An early diagnosis of infection helps to initiate adequate and timely measures and improves outcome of cirrhotic patients. Endocan is a newly recognized biomarker of sepsis. However, there have been no studies of the trends in endocan levels in cirrhotic patients with bacterial infection and their associations with markers of infection and inflammation. This study sought to assess the diagnostic value of serum levels of endocan, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in 126 patients with cirrhosis: 51 with decompensated infected cirrhosis, 56 with decompensated uninfected and 19 with compensated uninfected cirrhosis at inclusion. We analyzed the association of endocan with clinical factors in cirrhosis by comparison with indicators of infection and inflammation. Endocan, PCT, CRP, IL-6 and TNF-α were assayed in serum samples by ELISA analyses. Serum levels of endocan, PCT, CRP and TNF-α were significantly higher in cirrhotic patients with clinically overt infections. Endocan levels were correlated to neither PCT levels nor IL-6 levels in each group of patients with cirrhosis. CRP and TNF-α levels and Child-Pugh score correlated only in the infected group of patients with endocan levels, while in the uninfected groups of cirrhotic patients no significant correlation could be detected. The diagnostic accuracy of endocan increased in advanced stage of the disease. Serum endocan levels ≥ 2.05 ng/ml had a sensitivity of 76.1% and specificity of 85% for the diagnosis bacterial infection in decompensated cirrhotic patients. The endocan measured at admission is a good clinical parameter predicting the occurrence of infection in these patients. Elevated endocan may reflect the degree of endothelial cell injury induced by a systemic inflammatory response, a pathologic process that could modify the course of advanced cirrhosis.

Aim of the Study: To determine the influence of HBsAg and HBeAg negative but anti-HBc positive status on the sustained virological response (SVR) rate in HCV-infected patients treated with pegylated interferon alfa 2 (Peg-IFNα-2) and ribavirin (RBV)., Material and Methods: The study was based on the retrospective analysis of medical records of HCV-infected patients who started Peg-IFNα and RBV treatment between 1 January 2011 and 31 December 2013 at the 1 st and 2 nd Department of Infectious Diseases of the Regional Hospital in Wrocław, Poland., Results: Among 240 patients included in the analysis 99 were anti-HBc positive and 141 anti-HBc negative. In the genotype 1, anti-HBc positive group the SVR rate was 47% and in the anti-HBc negative group it was 42.7% ( p = 0.591). In the genotype 3, anti-HBc positive group the SVR rate was 60% and in anti-HBc negative patients it was 63.2% ( p = 0.79). Differences in SVR rates between anti-HBc positive and negative groups were not statistically significant. None of the anti-HBc positive patients developed reactivation of HBV infection during or in the 24 weeks following the end of treatment., Conclusions: Anti-HBc determination does not seem to be useful in predicting treatment outcome of conventional Peg-IFNα/RBV therapy in patients infected with HCV genotypes 1 and 3.

Appropriate nutrition - in terms of both quantity and quality - is not only one of the main life processes. A well-balanced diet including sufficient amounts of minerals and vitamins supports proper human development and functioning from fetal development to very advanced old age; it promotes regeneration after intensive exercise and is a key element for successful treatment of most acute and chronic diseases, including liver diseases.

Aim of the Study: To determine plausible associations between liver cirrhosis and circulating endothelial cell-derived microparticles (EMPs), vascular endothelial growth factor (VEGF) levels and plasma nitric oxide (NO) metabolites., Material and Methods: Sixty patients with cirrhosis and 20 healthy control subjects were enrolled in the study. Circulating EMPs from platelet-poor plasma samples were examined by flow cytometry. These microparticles were categorized into endothelial cell-derived activated MPs (EMP-ac) (CD31 + CD42b - AN-V - ) and endothelial cell-derived apoptotic MPs (EMP-ap) (CD31 + CD42b - AN-V + ). Plasma VEGF levels were measured by enzyme-linked immunosorbent assay. Plasma NO metabolites (NO x - ) levels were determined using a Greiss reaction method., Results: Compared with the healthy control subjects, the patients with cirrhosis showed a significant increase in plasma levels of both phenotypes of EMPs. When the presence of ascites was considered, the plasma levels of EMP-ap were higher ( p < 0.01), as well as NO x - ( p < 0.05). EMP-ap positively correlated with VEGF level in all cirrhotic patients and this correlation was stronger in decompensated cirrhotic patients. In multivariate logistic regression analysis, the independent factors associated with the presence of ascites were high EMP-ap levels and elevated VEGF levels., Conclusions: Elevated plasma levels of EMP-ap in addition to high levels of VEGF might be considered as valuable parameters for predicting the occurrence of ascites in cirrhotic patients., Competing Interests: Authors report no conflict of interest.

Haemophilia is an entity, wherein the HCV infection rate is greater than in the general population and ranges between 70-90%. The majority of HCV infections were acquired by hemophiliacs in the 1980s, by the use of infected cryoprecipitate or fresh frozen plasma preparations. It is therefore highly likely that many of them, more than twenty years after the infection, have developed advanced liver disease. Until recently, in order to assess its severity, it was necessary to perform a liver biopsy. Currently, we observe rapid developments of non-invasive methods that are particularly useful in patients with bleeding disorders. The most popular include elastography (Fibroscan, SWE) and the algorithms based on measurements of the relevant blood parameters (e.g. FibroTest, Fibrometer, APRI index). Ease of implementation of these studies, no need for hospitalization of the patient or specific preparation for surgery, allow for quick and minimally invasive assessment of liver disease progression and classification of the patient to the appropriate antiviral therapy.

Hepatocellular carcinoma is the fifth most common malignancy and the third leading mortality cause worldwide. It typically develops secondarily to liver cirrhosis, due to hepatitis B or C infection, alcohol abuse, metabolic disease, and so forth. According to the American Association for the Study of Liver Diseases (AASLD) guidelines, which constitute diagnostic standards, the diagnosis of primary hepatocellular carcinoma (HCC) should be based on contrast-enhanced imaging. Lesion hyperenhancement should be observed throughout the arterial phase, followed by the washout during the venous phase. The diagnosis can also be based on the histopathological evaluation of liver biopsy specimen. Although the standards are clear, we often see patients with advanced HCC in clinical practice, who cannot be offered any effective treatment. Patients with chronic liver disease, presenting with inconclusive and changeable test results, constitute a separate problem. In such cases the diagnostic process is typically long-term and delayed. In this paper we present three case reports where the diagnosis could not be made promptly and the patients died as a result of a delayed diagnostic process.

Aim: To investigate the relationship between advanced oxidation protein products (AOPPs) and myocardial injury by comparing the selected biomarker for detecting myocardial injury [high-sensitive troponin T (hs-TnT)] in patients with chronic HCV infection., Methods and Results: Eighty-eight patients with cirrhosis and 40 healthy control subjects were enrolled in the study. Circulating levels of AOPPs-albumin (the ratio of AOPPs to albumin content), hs-TnT, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were assessed. Compared with healthy controls, the cirrhotic patients with chronic HCV infection had higher levels of AOPPs-albumin, which were associated with increased hs-TnT. When the presence of ascites was considered, the plasma levels of AOPPs-albumin were higher, as well as TNF-α. AOPPs-albumin positively correlated with hs-TnT level in all cirrhotic patients with chronic HCV infection and this correlation was stronger in decompensated cirrhotic patients. In multivariate logistic regression analysis, the independent factors associated with the presence of ascites were high AOPPs-albumin levels and elevated hs-TnT levels., Conclusion: The simultaneous monitoring of plasma AOPPs and hs-TnT can be helpful for the alterations in myocardial function control in cirrhotic patients with chronic HCV infection.

Background: The human genome contains about 8% of endogenous retroviral sequences originated from germ cell infections by exogenous retroviruses during evolution. Most of those sequences are inactive because of accumulation of mutations but some of them are still capable to be transcribed and translated. The latter are insertionally polymorphic HERV-K113 and HERV-K115. It has been suggested that their presence and expression was connected with several human diseases. It is also believed that they could interfere with the replication cycle of exogenous retroviruses, including HIV., Results: Prevalence of endogenous retroviral sequences HERV-K113 and HERV-K115 was determined in the Polish population. The frequencies were found as 11.8% for HERV-K113 and 7.92% for HERV-K115. To verify the hypothesis that the presence of these HERVs sequences could affect susceptibility to HIV infection, comparison of a control group (HIV-negative, not exposed to HIV; n = 303) with HIV-positive patients (n = 470) and exposed but uninfected (EU) individuals (n = 121) was performed. Prevalence of HERV-K113 and HERV-K115 in the EU group was 8.26% and 5.71%, respectively. In the HIV(+) group we detected HERV-K113 sequences in 12.98% of the individuals and HERV-K115 sequences in 7.23% of the individuals. There were no statistically significant differences between groups studied., Conclusion: The frequency of HERV-K113 and HERV-K115 sequences in Poland were found to be higher than usually shown for European populations. No relation between presence of the HERVs and HIV infection was detected.

Based on investigations of liver biopsy material, certain cellular genes have been implicated as correlates of success or failure to interferon alpha-ribavirin (IFN/RBV) therapy against hepatitis C. The current study aimed at determining whether expression of host genes thought to be relevant to HCV replication in the liver would be correlated with HCV infection status in peripheral blood mononuclear cells (PBMCs) and also with patient responsiveness to IFN/RBV treatment. Therefore, PBMCs from patients with chronic hepatitis C responding (n = 35) or not (n = 49) to IFN/RBV and from healthy controls (n = 15) were evaluated for HCV RNA load and cellular gene expression. Non-responders had 3- to 10-fold higher basal levels of interleukin (IL)-8, IFN-stimulated gene 15 (ISG15), 2',5'-oligoadenylate synthetase (OAS), and Toll-like receptors (TLR)-4, -5, and -7 compared to responders. Non-responders with similar post-treatment follow-ups as responders persistently expressed 6- to 20-fold greater levels of IL-8, ISG15, and OAS after therapy. Higher expression of IFN-α, IFN-γ, and IFN-λ was found in PBMCs of individuals achieving sustained virological response, either before or after therapy. Pre-treatment HCV RNA loads in PBMCs of non-responders were significantly higher (P = 0.016) than those of responders. In conclusion, the data indicate that immune cells of responders and non-responders to IFN/RBV therapy exhibited significantly different virological and host gene expression profiles. Elevated baseline HCV loads and TLR-4, -5, and -7 levels, and persistently high levels of IL-8, ISG15, and OAS were correlated with IFN non-responsiveness. The results warrant further investigations on the utilization of PBMCs for predicting success or failure to IFN-based therapies., (Copyright © 2012 Wiley Periodicals, Inc.)

Effects of chemokine receptor alleles (CCR5-Δ32 and CCR2-64I) on susceptibility to human immunodeficiency virus (HIV) infection were studied in a Polish population. The CCR5 and CCR2 genotypes were determined for 311 healthy, HIV-negative individuals (control group), 121 exposed to HIV infection but uninfected (EU group), and 470 HIV-positive patients. The frequency of the alleles in the control group was calculated as 0.12 for both CCR5-Δ32 and CCR2-64I. The logistic regression method was used to analyze the effects of the described factors. A protective effect was observed for the CCR5-Δ32 allele but only in the case of heterosexual exposure. Prevalence of the CCR5-Δ32/+ genotype in HIV(+) patients infected via the heterosexual route (n=61; 8.2%) was much lower than in the control group (n=311; 21.5%); in the heterosexually exposed uninfected group it was slightly higher (n=28; 25%). This suggested that in this mode of infection, the native CCR5 expression level was crucial for establishment of infection. Individuals with the CCR5-Δ32 allele have more than three times less chance of infection in the case of HIV heterosexual exposure (odds ratio, 3.37; 95% confidence interval, 1.055-10.76). However, a protective effect of the CCR5-Δ32/+ genotype was not observed in the case of intravenous drug users (IDUs). The rates of the genotype were similar in HIV-infected IDU individuals (n=356; 17.7%) and in exposed uninfected patients (n=84; 15.5%), not significantly different from control group. No effect of the CCR2 genotype was observed. The analysis revealed that the important factor increasing infection risk was, in particular, hepatitis C virus (HCV) infection (odds ratio, 12.9). Moreover, the effect of HCV infection was found to be age dependent. Susceptibility to HIV infection resulting from HCV positivity became weaker (6% per year) with increasing age.

Primary hepatocellular carcinoma (HCC) is the most commonly diagnosed primary malignancy of the liver. The number of new diagnosed cases of HCC seems to be on a rise worldwide. HCC is typically diagnosed in patients with underlying liver cirrhosis (> 90% cases) regardless of aetiology; over a five-year follow-up period HCC develops in 15-20% of patients with cirrhosis. Patients who are at a high risk of HCC development (i.e. individuals with liver cirrhosis, especially/or chronically infected with HBV or HCV) should undergo regular screening for HCC; the current screening standard comprises liver ultrasonography and determination of α-fetoprotein (AFP) concentration in blood serum at ca. 6 months' intervals (now has been excluded from current diagnostic standards). Only such diagnostic methods are capable of detecting HCC early, and thus make it possible to treat the cancer effectively.

Macrophage activation seems to be a feature of chronic liver diseases. Picolinic acid (PA) as a macrophage secondary signal causes the activation of interferon-gamma- (IFN-γ-) prime macrophage and triggers cytokine-driven inflammatory reactions. The rationale for seeking increased PA formation in chronic viral hepatitis is based on the involvement of activated macrophages in chronic viral hepatitis-associated inflammation. The aim of this study was to determine serum PA levels in patients with chronic hepatitis C infection, taking into account the presence of diabetes. We assessed PA and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation in 51 patients with chronic hepatitis C infection (CHC), both with and without diabetes and 40 controls. Compared with the controls, the patients with CHC showed a significant increase in plasma concentrations of PA and hsCRP (P < 0.01 and P < 0.05, resp.). The values of PA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were between PA and hsCRP levels (P < 0.05) and the presence of diabetes (P < 0.001). We documented that significant elevation in serum PA levels is associated with diabetes prevalence and increased inflammatory response reflected in hsCRP levels in CHC patients.

Inflammation and oxidative stress have been reported in patients with chronic hepatitis C (CHC) infection, but their influence on ischemia-modified albumin (IMA) levels and diabetes prevalence remains unknown. Sixty-three CHC patients, 28 with diabetes, and 40 healthy controls were enrolled in the study. Circulating levels of oxidative stress markers [Nε-(carboxymethyl)lysine- advanced glycation end products (CML-AGEs) and advanced oxidation protein products-(AOPPs)], pro-inflammatory cytokines (interleukin-6, and tumor necrosis factor α), and high-sensitivity C-reactive protein (hsCRP) were assessed. Compared with the controls, the CHC patients with diabetes showed a significant increase in plasma concentrations of IMA, AOPPs, interleukin-6 and hsCRP (P < 0.05). The values of IMA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were found between hsCRP and presence of diabetes, IMA (both P < 0.01) and AOPP levels (P < 0.05). CML-AGEs did not show any significant correlation with IMA, markers of inflammation and presence of diabetes. In conclusion, we have documented significant elevation in plasma levels of IMA and AOPPs in CHC patients. In addition, circulating IMA was associated with inflammation markers and diabetes prevalence. This observation suggests a relationship between IMA and inflammation in CHC patients with diabetes, which may represent one of the mechanisms involved in the accelerated atherosclerosis in this population.

Advanced oxidation protein products (AOPPs) are protein markers of oxidative stress with pro-inflammatory properties that accumulated in liver cirrhosis. In the present study, we investigated the association between chronic inflammatory response triggered by AOPPs and the severity of liver disease as assessed by the Child-Pugh score. Plasma concentrations of AOPPs and inflammatory markers such as C-reactive protein, tumor necrosis factor-α, and interleukin-6 were measured in 41 patients with HCV-related cirrhosis, 43 patients with alcohol-related liver cirrhosis (ALC), and in 30 age and sex matched controls. In comparison with controls, AOPPs were increased in HCV-related compensated (Child-Pugh A) and decompensated (Child-Pugh B-C) cirrhosis and in alcohol-related compensated cirrhosis. AOPPs level positively correlated with Child-Pugh score in alcohol-related cirrhosis but not in HCV-related cirrhosis and the correlation with the indices of chronic inflammation was stronger in ALC. In turn, AOPPs in HCV-related cirrhosis was related to inflammation to a lesser extent, but a significant correlation with antioxidant defense could be noted. In summary, liver cirrhosis was associated with increased formation of AOPPs, which differed between alcohol-related and HCV-related cirrhosis with respect to the relationship between AOPPs and antioxidant defense, stage of liver cirrhosis, and inflammatory response. The significant correlation between AOPPs accumulation and indices of chronic inflammation, more specifically TNF-α, suggests that oxidative stress may be a mediator of chronic inflammatory state in the early stage of alcohol-related cirrhosis.

About 70% of HCV infection fail to resolve spontaneously and progress to chronic hepatitis C, eventually to cirrhosis and HCC. Many studies have demonstrated that clinical manifestation and the outcome of HCV infection are negatively influenced by a variety of cofactors and comorbidities. Moreover many of these cofactors often reduce the chance of achieving a sustained virological response (SVR) with only available combination therapy with pegylated interferon-alpha2 (PEG-IFN) and ribavirine (RBV). Dose modification of both currently licensed drugs for treatment of HCV infection and variations of treatment duration are the most discussed strategies to optimized the therapy, particulary in patients infected by genotype 1 HCV. Tailoring the duration of peginterferon/ribavirine therapy to HCV kinetics is useful to optimize the results of therapy.