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.

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.

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.

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.

Pigment epithelium-derived factor and matrix metalloproteinase-9 in liver cirrhosis.

BACKGROUND/AIM: The aim of this study was to assess the role of serum pigment epithelium-derived factor (PEDF) and matrix metalloproteinase-9 (MMP-9) in progression of liver cirrhosis and development of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Serum levels of PEDF and MMP-9 were tested in 212 patients with liver cirrhosis and in a control group of 30 healthy volunteers. HCC was diagnosed in 45 of the 212 patients studied (21%). RESULTS: Serum PEDF and MMP-9 were higher in the study group than that in the control group (P < 0.001). In patients with alcoholic or mixed (alcoholic and viral hepatitis-related) cirrhosis, serum PEDF was higher than that in other patients (13970.2 ± 13406.9 ng/ml vs. 8563.5 ± 9602.7 ng/ml, P = 0.008). In patients with viral hepatitis-related cirrhosis, significantly higher PEDF levels were recorded in those with HCC (13429.1 ± 12045.8) than that in patients without HCC (6660.1 ± 7927.1; P = 0.04). There was a trend for higher serum MMP-9 in patients with HCC (5778.7 ± 12426.6 vs. 1389.8 ± 1944.7 in those without HCC; P = 0.07). Significant negative correlation between serum MMP-9 and serum alpha-fetoprotein in patients with HCC was observed (r = -0.54; P = 0.04). CONCLUSION: Serum PEDF and MMP-9 could be auxiliary markers in diagnosis of HCC, especially in patients with low alpha-fetoprotein level. Alcohol consumption can affect serum PEDF.

Comparative analysis of the new chronic kidney disease epidemiology collaboration and the modification of diet in renal disease equations for estimation of glomerular filtration rate in HIV type 1-infected subjects.

Recently, a new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was presented as a better alternative to the modification of diet in renal disease (MDRD) formula for GFR estimation (eGFR) in patients with relatively well-preserved kidney function. The main objective of our study was to compare the eGFR results arrived by the new CKD-EPI to the older MDRD equation in antiretroviral (ARV)-naive and ARV-treated HIV-1-infected patients. The study was performed in 287 adult HIV-1-infected patients and was an evaluation comparing eGFR results based on age, gender, race, and serum creatinine. The biggest difference in estimated glomerular filtration rate (eGFR) measured by the two formulas was seen in ARV-naive men with well-preserved kidney function (p = 0.001). Moreover, we found a significant negative correlation between mean difference in eGFR measured by the two equations and the age of the studied subjects (r = -0.37, p < 0.001). No correlation was observed between mean difference in eGFR and HIV viral load (r = -0.15, p = 0.2). Independent of the equation used, a significant decrease of eGFR in ARV-treated in comparison to ARV-untreated HIV-1-infected patients was seen (p < 0.001). In conclusion, in HIV-1-infected subjects, especially in ARV-naive men with well-preserved kidney function, eGFR measured by MDRD and CKD-EPI formulas varies strongly following the method used. Such discrepancies may be important in everyday clinical practice and must be confirmed by additional studies using GFR measured with a reference method.