Magdalena Rogalska-Płońska

Prevalence of cryoglobulinaemia in hepatitis C virus- and hepatitis C virus/human immunodeficiency virus-infected individuals: implications for renal function.

Background and aims: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) demonstrate an affinity towards lymphocytes B, stimulating the production of cryoglobulins. Deposits of cryoprecipitates contribute to glomerulonephritis and renal failure. The presence of cryoglobulins was investigated in the sera of HCV‐monoinfected and HCV/HIV‐coinfected individuals. Associations between types of cryoglobulins and HCV genotypes, viral load and renal function tests were also evaluated.

Serum cytochrome c and m30-neoepitope of cytokeratin-18 in chronic hepatitis C.

Cytochrome c (CYC) and M30‐neoepitope of cytokeratin‐18 (M30‐CK18) are involved at different levels in apoptotic pathways. We aimed to evaluate an association between serum CYC, M30‐CK18 and disease activity as well response to therapy in chronic hepatitis C (CHC).

Influence of HCV and HIV on Development of Cryoglobulinemia

Cryoglobulinemic syndrome refers to a systemic inflammatory process that involves small and medium-sized vessels accompanied by multi-organ damage. The aim of the present study was to determine the incidence of cryoglobulinemia among patients infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HCV/HIV co-infection, as well as evaluation of cryoglobulinemia type. The association was evaluated between cryoglobulinemia and clinical symptoms, selected biochemical measures of liver and kidney function, virologic measures, as well as histopathological changes in the liver. One hundred and forty-one patients were enrolled (59 HCV mono-infected, 48 HIV mono-infected, and 34 HCV/HIV co-infected). Cryoglobulinemia was nearly five times less frequent among HIV mono-infected patients (10%) than HCV mono-infected (53%) and HCV/HIV co-infected patients (59%). Cryoglobulinemia was more frequent in patients infected with genotype 1 HCV than genotype 3 (63% vs. 46%, p=0.12). There was a lower incidence of cryoglobulinemia in HIV mono-infected patients treated with antiretroviral drugs (p=0.04). Cryoglobulinemia correlated with ALT activity (p=0.01) and HIV viral load (p<0.001). Symptoms were significantly more frequent among cryoglobulinemic patients than those without cryoglobulinemia (38% vs. 9%, p<0.001). The most common symptoms related to cryoglobulinemia, regardless of cryoglobulinemia type, were fatigue (38%), arthralgia (20%), polineuropathy (18%), and skin lesions (14%). In conclusion, HCV mono-infection and HCV/HIV co-infection, regardless of HCV genotype, are potent stimulators of cryoglobulinemia, with its symptomatic form occurring in about 40% of cases. Effective antiretroviral therapy seems to be protective against cryoglobulinemia development in HIV mono-infected patients.

Metabolic syndrome in HIV infected adults in Poland

BACKGROUND Metabolic syndrome (MS) is usually diagnosed based on the presence of abdominal obesity, elevated blood pres-sure (BP), elevated fasting plasma glucose, high serum triglycerides (TG), and low high-density lipoprotein (HDL) cholesterol levels. Whether HIV is associated with a higher prevalence of MS than in the general population remains unclear. AIM The aim of the study was to determine the incidence of MS in the population of HIV-infected adults and its association with clinical, virological, and biochemical features. METHODS Two hundred and seventy HIV-infected Caucasian adult patients were enrolled in the study and evaluated based on clinical records in the years 2013-2015. RESULTS Metabolic syndrome was diagnosed in 60 of 270 (22%) patients, 47 (24%) males and 13 (17%) females, mostly (72%) aged above 40 years. The percentage of patients with diagnosed MS in specific age groups in comparison to the general Polish population for females aged < 40 years was 7% vs. 4%, and males in the same age - 18% vs. 9%, for females aged 40-59 years - 47% vs. 24.4%, and males - 33% vs. 28.3%. Particular components of MS in the MS population were found as follows: body mass index > 30 kg/m2 in 29%, waist circumference exceeding 94 cm in men and 80 cm in woman - 87.5%, TG ≥ 150 mg/dL - 82%, HDL cholesterol < 40/50 mg/dL (males/females) - 42%, systolic/diastolic BP ≥ 130 mmHg/≥ 85 mmHg - 83%, and fasting glucose > 100 mg/dL - 42%. In stepwise multivariate logistic regression analysis, age (odds ratio [OR] 1.052, 95% con-fidence interval [CI] 1.018-1.088, p = 0.003) and nadir CD4 < 350 cells/mm3 (OR 3.576, 95% CI 1.035-12.355, p = 0.04) were associated with MS. Patients with MS compared with those without this disorder had low, intermediate, high, and very high cardiovascular risk in 10% vs. 23%, 73% vs. 70%, 7% vs. 5%, and 10% vs. 2%, respectively (p = 0.006). CONCLUSIONS Prevalence of MS in the HIV-infected population is higher than in the general Polish population. Age and low nadir CD4 were found to be associated with MS.

Significance of mutations in the region coding for NS3/4 protease in patients infected with HCV genotype 1b.

BACKGROUND Fast hepatitis C virus (HCV) replication is one of the reasons for frequent changes in viral genome. OBJECTIVES The objective of this study was to evaluate the frequency and type of mutation in NS3/4 protease in patients with HCV genotype 1b and to determine the effect of the mutation on viral load, fibrosis stage, alanine aminotransferase (ALT) activity, and alpha-fetoprotein (AFP) level. MATERIAL AND METHODS The study included 46 treatment-naïve patients, infected with HCV genotype 1b. Mutations were analyzed after isolating HCV RNA, and then evaluating the compliance of the amino acid sequence, using 3500 Genetic Analyzer (Applied Biosystems, Foster City, USA). RNA fragment from nucleotide 1-181 encoding NS3/4 protease was subjected to analysis. RESULTS Mutations were demonstrated in 65% of subjects. Changes in the protease region affecting resistance to treatment (T54, Q80, V158, M175, D186) were detected in 10.8% of patients. Substitution mutation at T72 was found most frequently - in 49.9% of cases. In 13% of patients, mutation at G86 was demonstrated, including G86P in 5 patients and G86S in 1 patient. In the group of patients with T72 mutation, viral load was significantly higher (1.3 × 106 IU/mL vs 1.0 × 105 IU/mL; p = 0.01), AFP level was higher and fibrosis level was lower (1.26 vs 2.17; p = 0.008) compared to the patients without the mutation. Cryoglobulinemia was observed in 74% of patients with mutation at position T72. CONCLUSIONS Natural mutations of the region coding for NS3/4 protease are found frequently in patients infected with genotype 1b, but they may cause resistance to antiviral agents only in 11% of patients. Changes were most frequently found at position T72. Mutations at position T72 are correlated with the cryoglobulinemia occurrence. This is a substitution mutation, accompanied by a high viral load, high ALT activity and AFP level, which may point to a more unfavorable influence of such a modified virus, compared to wild-type virus, onto pathological processes in the liver.

Serum Cytokeratin 18 M30 Levels in Chronic Hepatitis B Reflect Both Phase and Histological Activities of Disease

Chronic hepatitis B has highly a dynamic course with significant fluctuations of HBV-DNA and ALT impeding assessment of disease activity. New biomarkers of inflammatory versus noninflammatory stages of HBV infection are urgently needed. Cytokeratin 18 epitope M30 (M30 CK-18) is a sensitive marker of cell death. We aimed to investigate an association between serum M30 CK-18 and histological activity and phase of HBV infection. 150 Caucasian patients with HBV-infection were included in the study. Serum M30 CK-18 levels reflected phase of disease, being significantly higher in both HBeAg(+) and HBeAg(−) hepatitis B in comparison to HBsAg(+) carrier groups. The highest serum M30 CK-18 levels were observed in subjects with the most advanced stages of HBV. Moreover, its serum concentrations correlated with both inflammatory activity and fibrosis advancement (ANOVA P < 0.001). Importantly, serum M30 CK-18 levels were able to discriminate patients with mild versus moderate-advanced fibrosis (AUC: 0.86) and mild versus active liver inflammation (AUC: 0.79). M30 CK-18 serum concentration has good sensitivity and specificity in discriminating mild versus moderate/severe fibrosis and inflammation even in patients with normal ALT activity. This study suggests M30 CK-18 as a potential noninvasive marker of disease activity and also a marker of phase of persistent HBV infection.

Hypertension, dyslipidaemia, and cardiovascular risk in HIV-infected adults in Poland

BACKGROUND The prevalence of cardiovascular diseases (CVD) in HIV-infected patients increases with aging and duration of the disease. Hypertension, high cholesterol level obesity, diabetes, tobacco exposure, and use of alcohol are among the traditional risk factors that contribute to CVD. AIM The aim of the study was to determinate the incidence of hypertension, lipid disturbances, and CVD risk in dependence on clinical, viral, and biochemical factors. METHODS A total of 417 HIV-infected Caucasian adult patients from the four clinical centres in Poland were enrolled and analysed on the basis of available medical data from the years 2013-2015. RESULTS Hypertension was diagnosed in 28% of all patients and in the age ranges: < 40 years, 41-60 years and > 60 years in 18%, 43%, and 53%, respectively. The percentage of optimal, normal, and high normal blood pressure was: 28%, 14%, and 30%, respectively. Hypertension grade 1, 2, and 3 was observed in 58%, 35%, and 7% of patients, respectively. Factors associated with hypertension were: increasing age, male sex, increased body mass index, hypercholesterolaemia, hypo-high density lipoprotein (HDL), hypertriglyceridaemia and duration of HIV infection more than 10 years. Hypercholesterolaemia, suboptimal level of HDL, elevated low-density lipoprotein, and hypertriglyceridaemia were observed in 37%, 20.5%, 31%, and 52%, respectively. Hypertriglyceridaemia was associated with protease inhibitor-based highly active antiretroviral therapy. HCV infection was negatively associated with hypercholesterolaemia. Cigarette smoking was reported in 55% of cases. CONCLUSIONS Incidence of hypertension in particular age groups of HIV infected people is higher than in the general Polish population. Hypertension is influenced by traditional risk factors and duration of HIV infection but not antiretroviral treatment. HIV/HCV coinfection appears to be protective against hypercholesterolaemia.

The occurrence of autoantibodies in patients with chronic HCV infection, including patients dialyzed and after kidney transplantation

Introduction There are reports suggesting that hepatitis C virus (HCV) may stimulate the autoimmune process. Studies have been undertaken to evaluate the occurrence and type of autoantibodies in HCV-infected patients with and without immunosuppression. Results were analyzed according to HCV genotype, intensity of inflammation and liver fibrosis stage. Material and methods The study included 105 patients chronically infected with HCV, including 25 with immunological suppression administered for kidney disease or kidney transplantation. Blood samples were tested by immunoblotting for the presence of AMA-M2, SLA/LP, LKM-1, LC1, anti-F-actin, anti-desmin, anti-myosin, anti-gp210 and anti-sp100 autoantibodies, and ANA. All the patients were scored for autoimmune hepatitis. Results Autoantibodies were detected in 32.5% of patients without immunosuppression and in 16% with immunosuppression. Single types of autoantibodies were identified in 26% of patients. The most frequent ones were ANA (19%) and AMA-M2 (5.7%). The presence of antibodies in patients with genotype 1 was significantly higher in comparison to their occurrence in genotype 3. Autoimmune hepatitis was not diagnosed in any of the patients. Immunoglobulin G level was significantly higher in patients with detectable autoantibodies, compared to patients without antibodies (1.89 vs. 1.28 g/dl, p < 0.001). No correlation between fibrosis stage or intensity of inflammatory state and the frequency of antibodies was found. Conclusions The antibodies are significantly more frequent in patients without immunosuppression and in patients infected with genotype 1 than genotype 3. The presence of these autoantibodies is not associated with the development of autoimmune hepatitis. Higher level of immunoglobulin G in the serum correlates with the presence of autoantibodies.

Original article Impact of rs12979860 polymorphism on liver morphology in chronic HCV infection

Aim of the study To determine distribution of rs12979860 genotypes, their correlations with viral load as well as inflammatory activity and stage of liver fibrosis in patients infected with HCV genotype 1. Material and methods The study included 132 patients infected with HCV genotype 1b. Serum viral loads were obtained with the PCR method. Rs12979860 polymorphisms were determined by sequencing of PCR products. Liver biopsy was performed in all patients. Results CT, TT and CC alleles of rs12979860 polymorphism were detected in 58%, 20% and 22% of patients respectively. The highest viral load was observed in the TT and the lowest in the CC group (72.0 × 106 IU/ml vs. 2.1 × 106 IU/ml, p < 0.005). A significant correlation was demonstrated between patient’s age and inflammatory activity as well as degree of liver fibrosis. No association was found between liver histopathology and HCV viral load or rs12979860 genotypes. Conclusions There is an association between HCV viral load and rs12979860 polymorphism. Inflammatory activity and stage of liver fibrosis depend on age, but there is no relationship with rs12979860 genotypes and HCV viral load.

Wyniki leczenia przewlekłego zapalenia wątroby typu B entekawirem

Hepatitis B virus is a main cause of chronic hepatitis regarding 350 million people worldwide, leading to life-threatening conditions: liver cirrhosis and hepatocellular carcinoma. The worsening progress may be blocked or delayed by the effective therapy. Entecavir is an oral nucleoside analogue, safe and well tolerated, very effective inhibitor of HBV polymerase resulting in rapid viral suppression, histological improvement and ALT normalization. In several randomized, multicentre trials entecavir was effective in nucleoside-naïve and lamivudinerefractory patients, hepatitis B e antigen positive or negative as well as patients with decompensated liver cirrhosis.