Znaczenie polimorfizmu "IL28B" w odpowiedzi na leczenie interferonem pegylowanym α i rybawiryną przewlekłego zapalenia wątroby wywołanego genotypem 1b HCV

Wstęp: Leczenie przewlekłego zapalenia wątroby typu C (PZW-C) pegylowanym interferonem α (Peg-IFN) z ryba wiryną powoduje tzw. trwałą odpowiedź wirusologiczną (sustained virological response - SVR) u blisko 50% chorych. Odpowiedź ta ściśle zależy od HCV i czynników genetycznych chorego. Wykazano, że polimorfizm genu IL28B wiąże się z eradykacją wirusa i SVR. Cel: Zbadanie, czy wyniki leczenia PZW-C u chorych z regionu Polski Południowej zależą od wariantów genetycznych IL28B, a polimorfizm może być czynnikiem predykcyjnym SVR. Materiał i metody: Sto czterdzieści dwie osoby z PZW-C spowodowanym genotypem 1b HCV leczono standardowo PegIFN z rybawiryną przez 48 tygodni. Polimorfizmy rs12979860 IL28B (C/T) badano metodą PCR-RFLP. HCV-RNA i aktywność aminotransferazy alaninowej (ALT) w surowicy mierzono przed leczeniem i po 12, 48 i 72 tygodniach terapii. Wyniki: Wiremia HCV-RNA przed terapią i po 12-tygodniowym leczeniu była wyższa u chorych z genotypem T/C i T/T. Trwałą odpowiedź wirusologiczną osiągnęło istotnie więcej chorych z genotypem C/C (71,1%) w porównaniu z 41,4% z genotypem T/C i 23,5% T/T. Chorzy z genotypem C/C lepiej reagowali na leczenie w porównaniu z osobami z genotypami T/C i T/T, osiągali wyższe wskaźniki odpowiedzi wczesnej (12 tygodni), na koniec leczenia (48 tygodni) i SVR. Aktywność ALT nie różniła się istotnie podczas terapii pomiędzy grupami. Tolerancja leczenia była podobna i nie zależała od genotypów C/C, T/C i T/T. Wnioski: Wyniki badania potwierdziły zależność odpowiedzi na standardowe leczenie PZW-C spowodowanego genotypem 1b HCV od predyspozycji genetycznej chorego, jednak w przeciwieństwie do niektórych doniesień złe rokowanie obserwowano u homozygot T/T IL28B.Introduction: Treatment of chronic hepatitis C (CH-C) with peginterferon α (Peg-IFN) and ribavirin leads to a sustained virological response (SVR) in 50% of patients and depends on HCV and host factors. Polymorphism of the IL28B gene is associated with eradication of HCV and SVR. Aim: The objective of this study was to examine patients from the region of southern Poland and determine whether CH-C therapy depends on the genetic variants of IL28B and whether this polymorphism may predict SVR. Material and methods: One hundred forty-two patients with CH-C and the genotype 1b HCV were treated with PegIFN and ribavirin for 48 weeks. IL28B rs12979860 polymorphisms (C/T) were tested by PCR-RFLP. The HCV-RNA and alanine aminotransferase (ALT) levels were measured before treatment and after 12, 48 and 72 weeks. Results: Viral load before and after 12 weeks of therapy was higher in the genotypes T/C and T/T than in C/C. 71.1% of patients with the genotype C/C achieved SVR vs. 41.4% with the genotype T/C and 23.5% with T/T. Patients with the genotype C/C responded better to treatment as compared to subjects with the genotypes T/C and T/T, and achieved better early response (12 weeks), at the end of treatment (48 weeks) and SVR. Alanine aminotransferase activity was similar among the groups. Tolerance of therapy was similar and independent of the genotypes. Conclusions: The study confirmed the dependence of response to standard treatment of CH-C caused by the genotype 1b HCV on the patient's genetic predisposition. In contrast to some other reports, poor prognosis was observed in T/T homozygotes of IL28B

Intrahepatic expression of genes related to metabotropic receptors in chronic hepatitis

AIM: To screen for genes related to metabotropic receptors that might be involved in the development of chronic hepatitis. METHODS: Assessment of 20 genes associated with metabotropic receptors was performed in liver specimens obtained by punch biopsy from 12 patients with autoimmune and chronic hepatitis type B and C. For this purpose, a microarray with low integrity grade and with oligonucleotide DNA probes complementary to target transcripts was used. Evaluation of gene expression was performed in relation to transcript level, correlation between samples and grouping of clinical parameters used in chronic hepatitis assessment. Clinical markers of chronic hepatitis included alanine and aspartate aminotransferase, γ-glutamyltranspeptidase, alkaline phosphatase and cholinesterase activity, levels of iron ions, total cholesterol, triglycerides, albumin, glucose, hemoglobin, platelets, histological analysis of inflammatory and necrotic status, fibrosis according to METAVIR score, steatosis, as well as anthropometric body mass index, waist/hip index, percentage of adipose tissue and liver size in ultrasound examination. Gender, age, concomitant diseases and drugs were also taken into account. Validation of oligonucleotide microarray gene expression results was done with the use of quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The highest (0.002 < P < 0.046) expression among genes encoding main components of metabotropic receptor pathways, such as the α subunit of G-coupled protein, phosphoinositol-dependent protein kinase or arrestin was comparable to that of angiotensinogen synthesized in the liver. Carcinogenesis suppressor genes, such as chemokine ligand 4, transcription factor early growth response protein 1 and lysophosphatidic acid receptor, were characterized by the lowest expression (0.002 < P < 0.046), while the factor potentially triggering hepatic cancer, transcription factor JUN-B, had a 20-fold higher expression. The correlation between expression of genes of protein kinases PDPK1, phosphoinositide 3-kinase and protein kinase A (Spearman’s coefficient range: 0.762-0.769) confirmed a functional link between these enzymes. Gender (P = 0.0046) and inflammation severity, measured by alanine aminotransferase activity (P = 0.035), were characterized by diverse metabotropic receptor gene expression patterns. The Pearson’s coefficient ranging from -0.35 to 0.99 from the results of qRT-PCR and microarray indicated that qRT-PCR had certain limitations as a validation tool for oligonucleotide microarray studies. CONCLUSION: A microarray-based analysis of hepatocyte metabotropic G-protein-related gene expression can reveal the molecular basis of chronic hepatitis

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Similarities and differences in reflux disease between young and elder patients

Wstęp. Choroba refluksowa (GERD) jest częstym schorzeniem u osób w podeszłym wieku. Celem pracy było porównanie symptomów związanych z GERD i nasilenia zmian zapalnych u osób w podeszłym wieku i u młodszych pacjentów. Materiał i metody. Do badania włączono 60 chorych, w tym 30 osób w wieku &#8805; 65 roku życia oraz 30 osób w wieku < 65 roku życia. U wszystkich wykonano badanie gastroskopowe oraz 24-godzinne badanie pH-metryczne. Wyniki. Nie stwierdzono istotnych różnic pomiędzy grupami pod względem czasu trwania choroby, występowania GERD w rodzinie, spożywania alkoholu, palenia tytoniu. Osoby starsze częściej stosowały niesteroidowe leki przeciwzapalne, odczuwały łagodne dolegliwości i zgłaszały regurgitacje. Również średnia wartość wskaźnika BMI była większa. U osób starszych częściej stwierdzano przepuklinę rozworu przełykowego (53% vs. 26%), a w 24-godzinnej pH-metrii wykazano, że odsetek czasu, w którym pH wynosiło mniej niż 4,0 w pozycji leżącej był wyższy. Nie stwierdzono natomiast różnic pod względem stopnia nasilenia zmian zapalnych w przełyku, obecności powikłań GERD z wyjątkiem częściej stwierdzanej u osób starszych metaplazji Barretta (20% vs. 3%). Wnioski. Dolegliwości w przebiegu GERD u osób w podeszłym wieku częściej mają charakter łagodny. Częstość występowania zapalenia przełyku oraz parametry badania pH-metrycznego są podobne u osób młodych i pacjentów w podeszłym wieku.Background. Gastroesophageal reflux disease (GERD) is a common disorder in elderly people. The study aimed to find differences in the clinical manifestations, intensity of symptoms as well endoscopic and pH-metry findings between young and elder people with GERD. Material and methods. We examined two groups of patients: 30 people aged &#8805; 65 years and 30 people under 65 year old. Gastroscopy and pH-metry were performed in all patients. Results. No statistical differences in GERD duration, family history of GERD, alcohol intake as well cigarette smoking were found between groups. Elder people more frequently used non steroid anti-inflammatory drugs and reported mild symptoms. In this group more frequently regurgitations occurred. Also mean BMI was higher in this group. Hiatal hernia was present in 53% of older people and in 26% of younger group. We noticed no differences between two groups in presence of oesophagitis but higher frequency of esophageal intestinal metaplasia in elder people. 24-hour pH-metry showed that only the percentage of time with pH < 4.0 in supine position was significantly higher in elderly people. Conclusions. Elder people with GERD in comparison to young adults report mostly mild symptoms. 24-hour pH-metry parameters as well frequency of oeophagitis are similar in young and elder people

Correlation of the ALA-PDT Treatment Efficacy and the HPV Genotype Profile of Genital Warts after Cryotherapy Failure and Podophyllotoxin Therapy in Male Patients

Background: Genital warts are the manifestation of the human papillomavirus (HPV) infection, which may last for weeks or months before the clinical presentation. The primary aim of the study was the correlation of the DNA HPV genotypes eradication with the treatment response in male patients with persistent genital warts. Methods: Twenty-one male patients (age range: 22–58) after failure of cryotherapy and podophyllotoxin treatment were enrolled in the study. Genetic tests (Real Time - PCR method) analyzed the presence of DNA-HPV before and 6 months after four sessions (4 weeks apart) of photodynamic therapy with 5-aminolaevulinic acid (ALA-PDT). The treatment efficacy was evaluated before each PDT session and at the end of the study. Results: The single HPV DNA type was present in 15/21 of the patients (13/15 HPV6). The high-risk HPV types were found in 8/21 subjects, of which 6/8 had several types. Six months after four sessions of PDT, complete response was found in 16/21 (76.19%; p = 0.0007) of patients, and DNA HPV clearance was found in 66.67% (p = 0.03). The eradication rate differed among patients with primary low-risk and high-risk HPV types—76.92% (10/13; p = 0.0003) and 50% (4/8; p = 0.05) respectively. Conclusion: ALA-PDT is an effective treatment even after the failure of previous modalities. The persistence of clinical lesions and high oncological risk HPV types should be an indication for treatment prolongation

Skin manifestations of neuroendocrine neoplasms: review of the literature

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumours derived from peptidergic neurons and specialized neuroendocrine cells capable of secreting various peptides or amines. These cells may be present in endocrine tissue or diffused in the tissues of the digestive or respiratory system. The article reviews the characteristic features of NENs, with particular emphasis on skin manifestations, such as necrolytic migratory erythema (NME), tongue inflammation, angular cheilitis, venous thrombosis and alopecia in glucagonoma; “flushing”, “lion face”, pellagra skin symptoms, “scleroderma-like features without Raynaud’s phenomenon” in carcinoid tumours. The paper also presents the clinical picture of the neuroendocrine tumour of the skin – Merkel cell carcinoma. The aim of this study was to draw attention to the need for precise and comprehensive diagnosis of the patients, with particular emphasis on skin lesions as a revelator of neuroendocrine tumours. This management allows for the early implementation of appropriate treatment