Human Immunodeficiency Virus as a Risk Factor for Cardiovascular Disease.

The developments in HIV treatments have increased the life expectancy of people living with HIV (PLWH), a situation that makes cardiovascular disease (CVD) in that population as relevant as ever. PLWH are at increased risk of CVD, and our understanding of the underlying mechanisms is continually increasing. HIV infection is associated with elevated levels of multiple proinflammatory molecules, including IL-6, IL-1ß, VCAM-1, ICAM-1, TNF-α, TGF-ß, osteopontin, sCD14, hs-CRP, and D-dimer. Other currently examined mechanisms include CD4 + lymphocyte depletion, increased intestinal permeability, microbial translocation, and altered cholesterol metabolism. Antiretroviral therapy (ART) leads to decreases in the concentrations of the majority of proinflammatory molecules, although most remain higher than in the general population. Moreover, adverse effects of ART also play an important role in increased CVD risk, especially in the era of rapid advancement of new therapeutical options. Nevertheless, it is currently believed that HIV plays a more significant role in the development of metabolic syndromes than treatment-associated factors. PLWH being more prone to develop CVD is also due to the higher prevalence of smoking and chronic coinfections with viruses such as HCV and HBV. For these reasons, it is crucial to consider HIV a possible causal factor in CVD occurrence, especially among young patients or individuals without common CVD risk factors.

The prevalence of smoking cigarettes among HIV-infected patients after a decade. Single-center analysis.

OBJECTIVES: Smoking habit is known to be a risk factor for the development of multiple diseases and conditions, premature death, and worse quality of life. The prevalence of smoking in PLWH is 2-3 times higher than in the general population. The study aimed to evaluate how the prevalence of smoking has changed among PLWH over the past decade. METHODS: The data of n=204 PLWH hospitalized from November 2018 to November 2019 was analyzed. All patients filled out the survey including age, gender, the number of cigarettes smoked, the number of years as a smoker, and the impact of HIV diagnosis on the number of cigarettes smoked. The data was compared to a similar analysis performed in our department in 2009. RESULTS: The study showed a decrease in the prevalence of smoking among PLWH over the past decade. In comparison to 2009, a statistically significant (p<0.05) reduction in the number of smoking individuals among ever and never smokers was observed both in males and in females. CONCLUSIONS: The prevalence of smoking cigarettes among PLWH in our department has significantly decreased since 2009 but remains much higher than in the general population. Smoking cessation interventions provided by HIV care professionals are necessary and should be continued among PLWH.

Rapid-progressing progressive multifocal leukoencephalopathy in two patients newly diagnosed with HIV: case series and review of literature.

The JC Polyomavirus (JCPyV) is a virus of global distribution and is usually kept under control by the immune system. In patients with AIDS, a latent JCPyV infection can reactivate and develop into progressive multifocal leukoencephalopathy (PML). Around half of the patients with PML die within 2 years since the diagnosis, yet in rare cases, the disease advances significantly quicker and seems to be insusceptible to any medical actions. In our clinic, we observed two cases of such course in HIV-positive patients in the AIDS stage. On admission, both patients had mild neurological symptoms such as dizziness, vision disturbances, and muscle weakness. Both had extremely low CD4 lymphocyte count (7 cells/µL, 40 cells/µL) and high HIV-1 viral load (VL) (50,324 copies/ml, 78,334 copies/ml). PML was confirmed by PCR for JCPyV DNA in cerebrospinal fluid (CSF) coupled with clinical and radiological features. Despite receiving though antiretroviral (ARV) treatment paired with intra-venous (IV) steroids, the disease progressed rapidly with neurological manifestations exacerbating throughout the few weeks following the admission. Eventually, both patients developed respiratory failure and died within less than 3 months after the onset of the neurological symptoms. Even though such curse of the disease is not common, it should be a warning to all how deadly both PML and AIDS can be and remind doctors to offer testing even to asymptomatic patients.

Evaluation of Clinical Biomarkers Related to CD4 Recovery in HIV-Infected Patients-5-Year Observation.

Human Immunodeficiency Virus infection leads to the impairment of immune system function. Even long-term antiretroviral therapy uncommonly leads to the normalization of CD4 count and CD4:CD8 ratio. The aim of this study was to evaluate possible clinical biomarkers which may be related to CD4 and CD4:CD8 ratio recovery among HIV-infected patients with long-term antiretroviral therapy. The study included 68 HIV-infected patients undergoing sustained antiretroviral treatment for a minimum of 5 years. Clinical biomarkers such as age, gender, advancement of HIV infection, coinfections, comorbidities and applied ART regimens were analyzed in relation to the rates of CD4 and CD4:CD8 increase and normalization rates. The results showed that higher rates of CD4 normalization are associated with younger age (p = 0.034), higher CD4 count (p = 0.034) and starting the therapy during acute HIV infection (p = 0.012). Higher rates of CD4:CD8 ratio normalization are correlated with higher CD4 cell count (p = 0.022), high HIV viral load (p = 0.006) and acute HIV infection (p = 0.013). We did not observe statistically significant differences in CD4 recovery depending on gender, HCV/HBV coinfections, comorbidities and opportunistic infections. The obtained results advocate for current recommendations of introducing antiretroviral therapy as soon as possible, preferably during acute HIV infection, since it increases the chances of sufficient immune reconstruction.

VCAM-1 as a Biomarker of Endothelial Function among HIV-Infected Patients Receiving and Not Receiving Antiretroviral Therapy.

The Human Immunodeficiency Virus and retroviral therapy are both known risk factors for cardiovascular disease. It remains an open question whether HIV or ARV leads to increased arterial inflammation. The objective of this study was to investigate the changes in endothelial activation by measuring VCAM-1 levels among HIV-infected patients who were and were not treated with antiretroviral therapy. It is a retrospective study that included 68 HIV-infected patients, 23 of whom were never antiretroviral-treated, 15 who were ART-treated for no longer than a year, and 30 who were ART-treated for longer than a year. Blood samples were collected for biochemical analysis of the concentration of VCAM-1. The results show a statistically lower VCAM-1 level (p = 0.007) in patients treated with ART longer than a year (1442 ng/mL) in comparison to treatment-naïve patients (2392 ng/mL). The average VCAM-1 level in patients treated no longer than a year (1552 ng/mL) was also lower than in treatment-naïve patients, but with no statistical significance (p = 0.096). Long-term antiretroviral therapy was associated with the decline of VCAM-1 concentration. That may suggest the lowering of endothelial activation and the decreased risk of the development of cardiovascular disease among ARV-treated patients. However, VCAM-1 may not be a sufficient factor itself to assess this, since simultaneously there are a lot of well-known cardiovascular-adverse effects of ART.

Significance of Vascular Cell Adhesion Molecule-1 and Tumor Necrosis Factor-Alpha in HIV-Infected Patients.

BACKGROUND: The aim of this study was the evaluation of the correlation between VCAM-1 and TNF-alpha serum concentrations and various clinical and laboratory parameters in HIV-infected patients. METHODS: All included subjects were patients of the Department of Infectious and Tropical Diseases and Hepatology of the Medical University of Warsaw in Poland in the years 2014-2016. The inclusion criteria were: confirmed HIV infection, Caucasian origin, and age > 18 years old. PCT, CRP, serum HIV-1 RNA, CD4/CD8 T cell count, PCR HCV RNA, HBsAg, VCAM-1, and TNF-alpha were measured. The VCAM-1 and TNF-alpha serum levels were evaluated by ELISA. RESULTS: Seventy-two HIV-infected patients were included (16 women and 56 men: mean age 38.7 years, 66.6% cigarette smokers, 34.7% HCV co-infected HCV, and 27.8% ART-naïve). VCAM-1 concentrations were significantly higher in HIV/HCV co-infected patients than in HIV mono-infected patients (125.6 ± 85.4 vs. 78.4 ± 58.6 ng/mL, p = 0.011) and ART-naïve in comparison to patients on cART (121.9 ± 76.5 vs. 69.4 ± 57.1 ng/mL, p = 0.003). The significant positive correlation between HCV-infection and VCAM-1 and negative correlation between cART use and VCAM-1 was confirmed in multivariate analyses. The only variable associated significantly with TNF-alpha concentration was lymphocytes T CD8+ cell count (p = 0.026, estimate = 0.033). CONCLUSIONS: Successful cART and HCV eradication seemed to play an important role in the reduction of endothelial dysfunction and persistent inflammation in HIV-infected patients. CD8 T cell count seemed to be one of the markers of the pro-inflammatory state in HIV-infection patients.

Challenges in diagnosing fever in traveler returning from tropical ares - is it dengue or chikungunya? Case report.

Arthropod-borne viral infections caused by dengue virus (DENV) and chikungunya virus (CHIKV) are prevalent in the same regions and are spread by the same mosquito type (Aedes) and have similar clinical manifestations. This study emphasized the challenges of diagnosing fever in a patient returning from a tropical area. We report a case of a 52-year-old patient who presented with fever, myalgia, and headache after travelling to Laos and Thailand. After ten days of the disease, the diagnosis of chikungunya was made. Recent travel history should be a standard part of assessment when consulting febrile patients and is essential for further diagnosis. Malaria should permanently be excluded from travellers returning from tropical regions with fever. In the differential diagnosis, dengue, chikungunya, and other mosquito-borne infections should be considered. Patients wishing to travel to such areas need to be educated beforehand on the necessary preventative measures.

Five-Year Follow-Up of Cured HCV Patients under Real-World Interferon-Free Therapy.

(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.

Change in γ-glutamyl transpeptidase activity as a useful tool in identifying a group of patients with elevated risk of hepatocellular carcinoma development after DAA treatment of chronic hepatitis C.

AIM OF THE STUDY: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence will be diminishing due to use of direct acting antiviral agents (DAA), but there is still constant risk for HCC development. Elevated serum g-glutamyl transpeptidase (GGT) activity is associated with increased risk of liver cancer. In our study we tried to determine whether change in GGT activity may be useful in identifying patients with elevated risk of HCC development after DAA treatment. MATERIAL AND METHODS: The study population consisted of 111 patients with chronic hepatitis C (CHC) treated with DAA. Laboratory tests [alanine aminotransferase (ALT), GGT, a-fetoprotein (AFP)] and liver stiffness measurement (using FibroScan) were performed at the beginning and at the end of therapy. RESULTS: Pre-treatment ALT activity, GGT activity and AFP concentration in patients with CHC were directly associated with the stage of liver fibrosis. Elimination of HCV after DAA treatment caused significant reduction in serum GGT activity and was not associated with pre-treatment liver fibrosis. AFP concentration was significantly lower after treatment. It was observed regardless of pre-treatment AFP concentration, but the largest reduction was demonstrated in the group of patients with advanced fibrosis. In multivariate analysis there was no significant difference in GGT activity after treatment only in patients with pre-treatment normal AFP concentration and advanced liver fibrosis. CONCLUSIONS: Patients who after achieving a sustained virological response (SVR) did not lower both AFP concentration and GGT activity may have higher risk of HCC development. Special monitoring may be required in patients with advanced liver fibrosis and normal AFP concentration before treatment.

Cerebral Toxoplasmosis, CMV and Bacterial Pneumonia with Decreasing CD4+ T-Cell Count as Results of Antiretroviral Therapy Discontinuation-A Case Report.

Cerebral toxoplasmosis occurs mainly in immunocompromised hosts as a reactivation of latent Toxoplasma gondii infection. In the diagnostic process, magnetic resonance imaging (MRI), serum testing, and biopsy are used. We describe a case of a 43-year-old HIV-positive patient presenting with altered levels of consciousness, aphasia, and hemiparesis. The patient had a history of antiretroviral therapy discontinuation for about 3 years. MRI revealed lesions, suggesting cerebral toxoplasmosis and subacute hemorrhage, serum tests for Toxoplasma gondii were positive. Antiparasitics and glycocorticosteroids were administered. A decline in viral load and clinical improvement were observed, however CD4+ T-cell count continued to decrease. The patient's state worsened, he developed CMV and bacterial pneumonia, which led to his death. What is crucial in the management of an HIV-infected patient is effective and continuous antiretroviral therapy. Discontinuation of the treatment may result in AIDS and lead to poor recovery of the CD4+ T-cell population, even after reimplementation of antiretroviral therapy and a decrease in viral load.

Weight and body mass index increase after switch from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate-containing treatment in an antiretroviral therapy-experienced group.

Tenofovir alafenamide fumarate (TAF) is an alternative to tenofovir disoproxil fumarate (TDF). Currently, TAF is increasingly being used because of its non-inferior antiviral properties, lower risk of nephrotoxicity, and lower decrease in bone mineral density than TDF. There is growing evidence of unfavorable effects of TAF on weight and body mass index (BMI) in antiretroviral therapy (ART)-experienced patients treated with TAF-based ART. The aim of this study was to evaluate whether switching from TDF-containing to TAF-containing ART is associated with an increase in BMI and body weight in ART-experienced patients. Two study groups were established: 32 patients who switched from TDF to TAF only and 68 patients who switched from TDF to TAF along with changes to other components of the ART regimen. Significant weight gain and BMI increase was observed during the first year after initiation of TAF-containing ART regimens in both groups (mean change +1.91 kg and +0.61 kg/m2 in the first group and +1.50 kg and +0.49 kg/m2 in the second group). During the second year of TAF-based treatment, a sustained trend of body weight and BMI increase was noted only in the second group (mean change +1.46 kg, + 0.46 kg/m2). Analysis of body weight changes in certain subpopulations from the second group (selected based on patients' baseline characteristics) revealed a significant weight gain within two years after the switch in patients over 50 years old and in those whose ART had lasted longer than 10 years. These findings suggest that a possible impact of TAF on weight gain should be taken into account when selecting ART components, especially in older patients or those with a long history of antiretroviral treatment.

Risk Factors of Hypovitaminosis D in HIV-Infected Patients on Suppressive Antiretroviral Therapy.

Low serum vitamin D levels are very common in human immunodeficiency virus (HIV)-infected patients. In our cross-sectional study, we investigated the association between 25-hydroxyvitamin D (25(OH)D) levels and serum inflammation markers [C-reactive protein (CRP), white blood cells (WBC), D-dimers, platelet count (PLT)] in 148 HIV-infected patients on combined antiretroviral therapy [28 on tenofovir alafenamide (TAF)] and 40 healthy controls. The controls were significantly older (56.6 ± 19.1 years for HIV(-) vs. 45.1 ± 11.8 years for HIV(+); p = .001) and more females were observed in this group (65% for HIV(-) vs. 16.7% for HIV(+); p = .001). The vitamin D serum level was comparable in the two studied groups (74.2 ± 35.9 nmol/L for HIV(+) vs. 78.0 ± 27.6 nnmol/L for HIV(-), p = .545). In HIV-infected group, a significant positive correlation between CD4+ cell percentage and vitamin D level was observed (r = 0.17; p = .036). Furthermore, the significant negative correlation between vitamin D level and CD8+ cell percentage, PLT, CRP, and D-dimers was seen. In univariate analysis, only TAF use and AIDS status was associated with vitamin D level deficiency. No other antiretroviral (ARV) drug nor gender or smoking had influence on vitamin D serum level. In multivariate analysis, only AIDS status and CRP level were correlated with vitamin D level (slope estimate = 11.6 and p = .032 and slope estimate = -0.83 and p = .002; respectively). In summary, we report that low vitamin D level may be associated with high CRP level in HIV-infected patients on suppressive antiretroviral therapy, especially in AIDS phase. More larger studies are required to assess our observation concerning TAF use and vitamin D level in HIV-positive patients.

Hepatopathy of unknown etiology - is liver biopsy a good tool in differential diagnosis?

INTRODUCTION: Liver biopsy is a well-known method for the diagnosis and evaluation of chronic diffuse liver diseases, especially among patients with "hepatopathy of unknown origin". MATERIAL AND METHODS: In the years 2014-2015 we performed 259 liver biopsies in 28 patients (22 females, 6 males, aged 18-65 years, mean: 45 years) with an initial diagnosis of "hepatopathy of unknown origin". The liver biopsies of these 28 patients were revised by two independent pathologists. RESULTS: Histopathological features of autoimmune conditions were found in 11 cases, steatohepatitis with/without Mallory bodies in 7, simple steatosis without inflammation in 2 cases. In the other 8 cases the histopathological features were non-specific but pointed to vanishing bile duct syndrome, hemochromatosis, acute inflammation or fibrosis without inflammation. Surprisingly, only mild fibrosis without inflammatory infiltrates was present in one patient with a high titer of antinuclear antibodies (ANA > 1 : 3200). Mild cholestasis with bilirubinostasis was found in 4 cases. One patient had prominent lobular iron deposits and is now under observation for hemochromatosis. Vanishing bile duct syndrome as ductopenia without any signs of inflammation was found in one patient with suspicion of primary biliary cirrhosis. In one liver biopsy specimen we found normal liver architecture without inflammation or steatosis in a patient with elevated ALT and GGT, negative for viral antibodies and autoantibodies. CONCLUSIONS: Liver biopsy - despite the increasing access to new, non-invasive methods - remains a useful method in the differential diagnosis of liver diseases.

Mild hyperbilirubinemia as a marker of oesophageal varices in HCV-related compensated cirrhotic patients.

The natural course of compensated liver cirrhosis caused by chronic hepatitis C virus (HCV) infection is still a very interesting problem in hepatology. The prognostic usefulness of the Child-Pugh and MELD score in compensated liver cirrhosis is still debated. Consequently, several attempts have been made to determine parameters other than included in the Child-Pugh score, which could be helpful in the prognosis of compensated liver cirrhosis assessment. AIM: The aim of study was to identify a clinical or laboratory markers correlated with higher risk of liver decompensation among HCVinfected patients with compensated liver cirrhosis and presence or absence of esophageal varices. MATERIALS AND METHODS: The study included 176 HCV-infected patients with compensated liver cirrhosis (74 women and 102 men) registered in the Clinical Database of Patients with Liver Cirrhosis - e-Hepar. All patients were monitored during 252 weeks for the occurrence of liver failure symptoms and the development of hepatocellular carcinoma (HCC). RESULTS: The presence of esophageal varices was significantly associated with total bilirubin ≥2.0 mg/dl, platelets ≤110.0 G/L and 6 points in Child-Pugh score (p<0.05). The cumulative 252 weeks incidence of clinical decompensation was higher in patients with varices in comparison to patients without them (p<0.05). Variceal hemorrhages were observed in 9 cases (23.1%). During the follow-up period 9 patients died due to HCC complications. CONCLUSIONS: Our findings underline the prognostic value of serum bilirubin (even mild elevation) and platelet count in HCV-infected patients with compensated liver cirrhosis. We have confirmed that liver decompensation is more frequent and more rapid in patients with compensated liver disease and concomitant oesophageal varices.

Hepatocellular carcinoma after direct-acting antivirals: an unresolved problem. Review of five cases.

AIM OF THE STUDY: To present the problem of hepatocellular carcinoma (HCC) occurring in patients treated with direct-acting antiviral (DAA) agents and to draw attention to the fact that HCC may develop even after successful therapy and in patients who were not previously diagnosed with it. MATERIAL AND METHODS: The inclusion criterion was confirmation of successful DAA treatment prior to HCC among hepatitis C virus (HCV)-infected patients with liver cirrhosis. The analysed group consisted of 5 patients. RESULTS: In three patients the emergence of hepatocellular carcinoma was very rapid. They developed sudden decompensation of liver function with its symptoms - ascites, oedema, coagulation dysfunction. Furthermore, they had liver encephalopathy and renal failure. One of the patients had cancer cell thrombosis. Two patients' status was stable, but they were disqualified from liver surgery due to large size of the focal lesions and their plurality. CONCLUSIONS: DAAs, despite their high effectiveness in HCV treatment, still bear the risk of developing HCC. Patients after the therapy should remain under medical control for the early detection and treatment of the presumptive cancer.

Significance of Heparin-Binding Protein and D-dimers in the Early Diagnosis of Spontaneous Bacterial Peritonitis.

OBJECTIVES: Ascites and spontaneous bacterial peritonitis (SBP) are among the most important complications of decompensated liver cirrhosis. In clinical practice, new inflammation biomarkers are needed for the early diagnosis of SBP, as well-known biomarkers, such as C-reactive protein (CRP), procalcitonin (PCT), or peripheral blood white blood cell (WBC) count, lack the required specificity and sensitivity. The aim of the study was to evaluate the significance of heparin-binding protein (HBP) in comparison to CRP, PCT, WBC, and D-dimers in the diagnosis of SBP. DESIGN: Cross-sectional descriptive single-center study. SETTING: Department of Infectious and Tropical Diseases and Hepatology, Medical University of Warsaw, Poland. PATIENTS: All patients admitted to the aforementioned department with decompensated liver cirrhosis and ascites between February 1, 2016, and June 30, 2017. INTERVENTION: Several markers (HBP, CRP, PCT, WBC, and D-dimers) were analysed in blood serum in regard to their potential use in the diagnosis of SBP in patients with decompensated liver cirrhosis and ascites. We correlated the levels of the aforementioned markers with an ascitic fluid polymorphonuclear count using simple linear regression and multiple linear regression. Sensitivities, specificities, and positive and negative predictive values for SBP were calculated for the aforementioned makers of inflammation. MEASUREMENTS AND MAIN RESULTS: A total of 63 patients with decompensated liver cirrhosis and ascites participated in the study. The etiology of liver cirrhosis was varied (HCV: n = 40, HBV: n = 13, HCV/HBV: n = 4, AIH: n = 3, PBC: n = 2, and haemochromatosis: n = 1). After the peritoneal tap, 31 patients were determined to have SBP (defined as an ascitic fluid polymorphonuclear count > 250 cells/µL) and 32 patients had no evidence of SBP on peritoneal tap. A very weak, but statistically significant, correlation of HBP, WBC, and D-dimer levels with the peritoneal fluid polymorphonuclear (PMN) count was observed in the simple regression model, but multivariable analysis using the multiple regression model showed that only D-dimers correlated with peritoneal fluid PMNs independently from other inflammation biomarkers. A D-dimer cutoff value of 1500 ng/mL was determined optimal for ruling out SBP due to high sensitivity (96.8%) and a high negative predictive value (92.9%), although predictably, this marker was not useful for confirming SBP due to low specificity (40.6%) and a low positive predictive value (61.2%). The usefulness of D-dimers was limited by the fact that only 22.2% of the studied patients had D-dimer levels below 1500 ng/mL. HBP and WBC showed little to no predictive value in this study. CONCLUSIONS: D-dimers < 1500 ng/mL make the diagnosis of SBP unlikely, although the peritoneal tap is still the reference method in such situations. In the studied group, the determination of HBP was of no diagnostic benefit in the diagnosis of SBP.

Serum ADAMTS-13 Levels as an Indicator of Portal Vein Thrombosis.

BACKGROUND: Coagulation disorders in patients with liver cirrhosis are a common clinical problem. Cirrhosis should be considered a state of impaired blood clotting or an imbalance of the whole coagulation system. Cirrhosis-induced coagulopathy encompasses disturbances in both the procoagulant and anticoagulant systems. This mechanism may promote the development of thrombosis with portal vein thrombosis (PVT), which is considered an obstacle to orthotopic liver transplantation (OLT). We assessed serum ADAMTS-13 levels in patients with decompensated liver cirrhosis, with and without PVT. MATERIAL AND METHODS: Serum ADAMTS-13 levels, age, platelet count (PLT), and INR (international normalized ratio) were evaluated in (n = 64) patients with liver cirrhosis either with PVT (group 1, n = 31) or without PVT (group 2, n = 33). The results were compared with those from healthy volunteers (group 3, n = 37). Liver cirrhosis was based on Desmet's classification of chronic hepatitis in liver biopsy stage ≥ 3 or liver elastography F-score ≥ 3. Serum ADAMTS-13 levels were measured with Quantikine® ELISA Human ADAMTS13 Immunoassay, R&D Systems Inc. We used Welch's F-test, Games-Howell, one-way ANOVA, Bonferroni test, and logistic regression to determine whether ADAMTS-13 levels were a predictor that was independent of MELD and Child-Pugh scores. All results (P < 0.05) were considered statistically significant. RESULTS: The mean serum ADAMTS-13 level in patients with PVT was significantly lower than that in patients without PVT (P = 0.001) and controls (P = 0.001). The mean serum ADAMTS-13 level in patients without PVT was significantly lower than that in controls (P = 0.001). ADAMTS-13 levels were significantly associated with PVT accounting for the Child-Pugh or MELD score in the logistic regression model. CONCLUSIONS: Low serum ADAMTS-13 levels can be a useful indicator of portal thrombosis in patients with decompensated liver cirrhosis irrespective of Child-Pugh or MELD scores. Further research is needed to determine whether ADAMTS-13 levels will find use in everyday clinical practice.

Meeting the WHO 90% target: antiretroviral treatment efficacy in Poland is associated with baseline clinical patient characteristics.

INTRODUCTION: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. M: ethods Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients' characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used. RESULTS: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01-2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR:1.47 (95%CI:1.08-2.01), p = 0.016], baseline lymphocyte CD4 count ≥200 cells/µL [OR:1.72 (95%CI:1.04-2.78), p = 0.034] and negative HCV serology [OR:1.97 (95%CI:1.29-2.94), p = 0.002]. For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count ≥200 cells/µL [OR:2.08 (95%CI:1.01-4.35), p = 0.049] and negative HCV status [OR:2.84 (95%CI:1.52-5.26), p = 0.001]. CONCLUSIONS: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions.

The effects of CD4 nadirs on vessel stiffness in HIV patients undergoing antiretroviral therapy.

BACKGROUND: There are many factors associated with human immunodeficiency virus (HIV) patients having a greater risk of cardiovascular diseases (CVD). HIV damages vessel endothelium through chronic inflammation, which, combined with dys-lipidaemia, arterial hypertension, and antiretroviral therapy leads to the progression of atherosclerotic changes. AIM: Our goal was to determine if a CD4 nadir along with immunological, inflammatory, biochemical, and metabolic mark-ers can be associated with higher vessel stiffness and therefore an increased risk of CVD in patients undergoing antiretroviral therapy for HIV. METHODS: Endothelial damage was evaluated in 20 patients (including four female) during successful antiretroviral therapy. We assessed the endothelial stiffness by recording the reactive hyperaemia of peripheral arteries using an Endo-PAT2000 (ITAMAR®) device. This device allowed us to measure the arterial tonometry and to determine the augmentation index for a pulse rate of 75/min (AI@75). We set the normal value for vessel stiffness at reactive hyperaemia index (RHI) > 1.67, as recommended by the manufacturer. Additionally, we recorded the length of antiretroviral therapy, number of CD4 lymphocytes, CD4 nadir, HIV viremia, and biochemical and immunologic results. Finally, we compared patients with normal and dysfunctional endothelium. RESULTS: The only parameter significantly differentiating between the group with and group without endothelium dysfunction was platelet count (p = 0.012). CONCLUSIONS: We were not able to confirm the significance of a CD4 nadir in the progression of endothelial stiffness in HIV patients. However, platelet values could be an important complementary marker for assessing the risk for CVD amongst HIV patients undergoing antiretroviral treatment.