Monika Pazgan-Simon

Frequency of human endogenous retroviral sequences (HERV) K113 and K115 in the Polish population, and their effect on HIV 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.

Inhibition of vesicular stomatitis virus replication in the course of HIV infection in patients with different stages of immunodeficiency.

The replication of vesicular stomatitis virus (VSV) in isolated human leukocytes has been used to measure the level of nonspecific antiviral immunity. However, during infection with some pathogens, the main effect observed is caused by interaction between the pathogen and VSV. This was also noted in advanced stages of HIV infection, when an inverse association between HIV viral load and VSV replication was found. The mutual effect was markedly stronger than the correlation between the VSV replication level and CD4(+) T-cell count. Since successful antiretroviral therapy is associated with a decrease in HIV viremia to undetectable levels, the effect of such therapy on VSV replication was expected and confirmed in this investigation. In fact, increased VSV titers were observed together with decreased HIV viral load, particularly in the case of efficient therapeutic schemes, for example those including lopinavir/ritonavir. The results showed that VSV replication capacity reflected the progression of HIV infection. Moreover, the presence of interferon in the plasma of AIDS patients was found to be only partially responsible for the inhibition of VSV replication. The results suggest a specific HIV-VSV interaction, whether direct or indirect. Thus the VSV replication assay may be applied in evaluating the stage of HIV infection.

DRESS syndrome as a complication of treatment of hepatitis C virus-associated post-inflammatory liver cirrhosis with peginterferon α2a and ribavirin.

Various skin and systemic symptoms may develop as a complication of treatment with different medications and medicinal substances. One of them is a relatively rare drug reaction with eosinophilia and systemic symptoms, referred to as DRESS syndrome. The morphology of skin lesions and the patients general health can differ; the management involves withdrawal of drugs suspected of triggering DRESS syndrome, and administration of local and systemic glucocorticosteroids. In this paper we present a case of a patient with HCV associated chronic hepatitis, treated with peginterferon α2a (PEG-IFN-α2a) and ribavirin, who developed skin lesions and systemic symptoms typical of DRESS syndrome.

Picolinic Acid in Patients with Chronic Hepatitis C Infection: A Preliminary Report

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.

The risk of complications of endoscopic procedures in patients with liver cirrhosis

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.

The influence of anti-HBc status on the sustained virological response rate in HCV-infected patients treated with pegylated interferon alfa 2 and ribavirin

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 1st and 2nd 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.

Diagnostic Challenges in Primary Hepatocellular Carcinoma: Case Reports and Review of the Literature

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.

Increased Circulating Advanced Oxidation Protein Products and High-Sensitive Troponin T in Cirrhotic Patients with Chronic Hepatitis C: A Preliminary Report.

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.

Surveillance programmes for early detection of hepatocellular carcinoma

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.

Hepatitis B virus treatment in hepatocellular carcinoma patients prolongs survival and reduces the risk of cancer recurrence

Chronic hepatitis B virus (HBV) infection and HBV-related liver disease are estimated to affect about 240 million people worldwide. Now that a vaccine is available, the number of new HBV infection cases has plummeted. Yet, there are still regions with very high incidence of HBV. Hepatocellular carcinoma (HCC) is the fourth to six most common malignancy in men and the ninth most common malignancy in women worldwide. 54% of all HCC cases are HBV-associated, making it the most common cause of cancer worldwide. Hepatitis B therapy prevents progression of chronic hepatitis to cirrhosis and HCC development, but even with the best HBV treatment, such patients are still at risk of HCC. Also in patients after transarterial chemoembolization (TACE), liver resection (hepatectomy) or liver transplant, suppression of hepatitis B virus (HBV) improves patient survival. In this paper we present current possibilities of HCC and HBV treatment, which lead to improved survival and quality of life.