[Show abstract][Hide abstract] ABSTRACT: Previous studies have shown that single nucleotide polymorphisms (SNP) in IL28B and IL10R are associated with sustained virological response (SVR) in chronic hepatitis C patients treated with pegilated interferon plus ribavirin (P/R). The present study extends our earlier investigations on a large East-Central European cohort. The allele frequencies of IL28B and IL10R in genotype 1 HCV infection were compared with that of healthy controls for the purpose of examining the relationship between the polymorphisms and the SVR to P/R treatment.
A total of 748 chronic HCV1 infected patients (365 male, 383 female; 18-82 years) and 105 voluntary blood donors as controls were enrolled. Four hundred and twenty HCV patients were treated with P/R for 24-72 weeks, out of them 195 (46.4%) achieved SVR. The IL28 rs12979860 SNP was determined using Custom Taqman SNP Genotyping Assays. The IL10R -1087 (also known as IL10R -1082 (rs1800896) promoter region SNP was determined by RT-PCR and restriction fragment length polymorphism analysis.
The IL28B CC genotype occurred with lower frequency in HCV patients than in controls (26.1% vs 51.4%, p<0.001). P/R treated patients with the IL28B CC genotype achieved higher SVR rate, as compared to patients with CT (58.6% vs 40.8%, p=0.002). The prevalence of IL10R -1087 GG genotype was lower in patients than in controls (31.8 % vs 52.2%, p<0.001). Among patients achieving SVR, the IL10R -1087 GG genotype occurred with higher frequency than the AA (32.0% vs 17.4%, p=0.013). The IL28B T allele plus IL10R A allele combination was found with higher prevalence in patients than in controls (52% vs 20.7%, p<0.001). The IL28B CC plus IL10R A allele combination occurred with higher frequency among patients with SVR than in non-responders (21.3% vs 12.8%, p=0.026). Both the IL28B CC plus IL10R GG and the IL28B CC plus IL10R A allele combinations occurred with lower frequency in patients than in controls.
In our HCV1 patients, both the IL28B CC and IL10R GG genotypes are associated with clearance of HCV. Moreover, distinct IL28B and IL10R allele combinations appear to be protective against chronic HCV1 infection and predictors of response to P/R therapy.
BMC Research Notes 01/2014; 7(1):12. DOI:10.1186/1756-0500-7-12
[Show abstract][Hide abstract] ABSTRACT: Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications.
Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients.
CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40 KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores (N = 1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50 IU/mL] by week 4 of treatment (rapid virologic response) and 24 weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR (p < 0.1 × 10(-30)) was stronger than that between METAVIR (p = 3.86 × 10(-13)) or APRI (p = 5.48 × 10(-6)) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio.
The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40 KD)/ribavirin.
Hepatology International 01/2014; 8(1). DOI:10.1007/s12072-013-9484-6 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: In chronic hepatitis C-virus infection the possible role of gene variants encoding cytokines has become the focus of interest. Aim: The aim of the study was to investigate the effect of IL28B polymorphisms on the outcome of chronic hepatitis C-virus genotype 1 infection in the Hungarian population. In addition, the association between IL28B genotypes and the Th1/Th2 cytokine production of activated peripheral blood monocytes and lymphocytes was evaluated. Method: Total of 748 chronic hepatitis C-virus genotype 1 positive patients (365 males and 383 females, aged between 18 and 82 years; mean age, 54±10 years) were enrolled, of which 420 patients were treated with pegylated interferon plus ribavirin for 24-72 weeks. Of the 420 patients, 195 patients (46.4%) achieved sustained virological response. The IL28B rs12979860 polymorphism was determined using Custom Taqman SNP Genotyping Assays (Applied Biosystems, Life Technologies, Foster, CA, USA). For cytokine studies, tumour necrosis factor-α, interleukin-2, interferon-γ, interleukin-2 and interleukin-4 production by LPS-stimulated monocytes and PMA-ionomycine activated lymphocytes were measured from the supernatant of the cells obtained from 40 hepatitis C-virus infected patients, using FACS-CBA Becton Dickinson test. The cytokine levels were compared in patients with different (CC, CT, TT) IL28B genotypes. Results: The IL28B rs12979860 CC genotype occurred in lower frequency in hepatitis C-virus infected patients than in healthy controls (26.1% vs 51.4%, OR 0.333, p<0.001). Patients carried the T allele with higher frequency than controls (73.9%, vs 48.6%, OR 3.003, p<0.001). Pegylated interferon plus ribavirin treated patients with the IL28B CC genotype achieved higher sustained virological response rate than those with the CT genotype (58.6% vs 40.8%, OR 2.057, p = 0.002), and those who carried the T allele (41.8%, OR1.976, p = 0.002). LPS-induced TLR-4 activation of monocytes resulted in higher tumour necrosis factor-α production in patients with the IL28B CC genotype compared to non-CC individuals (p<0.01). Similarly, increased tumour necrosis factor-α, interleukin-2 and interferon-γ production by lymphocytes was found in the IL28B CC carriers (p<0.01) Conclusions: The IL28B CC genotype exerts protective effect against chronic hepatitis C-virus infection and may be a pretreatment predictor of sustained virological response during interferon-based antiviral therapy. The IL28B CC polymorphism is associated with increased Th1 cytokine production of activated peripheral blood monocytes and lymphocytes, which may play a role in interferon-induced rapid immune control and sustained virological response of pegylated interferon plus ribavirin treated patients. Orv. Hetil., 2013, 154, 1261-1268.
Orvosi Hetilap 08/2013; 154(32):1261-8. DOI:10.1556/OH.2013.29680
[Show abstract][Hide abstract] ABSTRACT: Introduction: Management of hepatitis C virus recurrence is a challenge after liver transplantation. Aim: The aim of the authors was to analyse the outcome of liver transplantation performed in hepatitis C virus positive patients during the past ten years and to compare recent data with a previous report of the authors. Method: The authors retrospectively evaluated the data (donors, recipients, perioperative characteristics, patient and graft survival, serum titer of hepatitis C virus RNA, histology) of 409 patients who underwent liver transplantation between 2003 and 2012. Results: 156 patients were transplanted due to hepatitis C virus associated liver cirrhosis (38%). Worse outcome was observed in these patients in comparison to hepatitis C virus negative recipients. The cumulative patient survival rates at 1, 5, and 10 year were 80%, 61%, 51% in the hepatitis C virus positive group and 92%, 85%, 79% in the hepatitis C virus negative group, respectively (p<0.001). The cumulative graft survival rates at 1, 5 and 10 year were 79%, 59% and 50% in hepatitis C virus positive and 89%, 80% and 70% in hepatitis C virus negative patients (p<0.001). Hepatitis C virus recurrence was observed in the majority of the patients (132 patients, 85%), mainly within the first year (83%). The authors observed recurrence within 6 months in 71 patients (56%), and within 3 months in 26 patients (20%). The mean hepatitis C virus recurrence free survival was 243 days. Higher rate of de novo diabetes was detected in case of early recurrence. The cumulative patient survival rates at 1, 3, 5, 10 years were 98%, 89.5%, 81% and 65% when hepatitis C virus recurrence exceeded 3 months and 64%, 53%, 30.5% and 30.5% in patients with early recurrence (p<0.001). Conclusions: Poor outcome of liver transplantation in hepatitis C virus positive patients is still a challenge. Hepatitis C virus recurrence is observed earlier after liver transplantation in comparison with a previous report of the authors. De novo diabetes occurs more frequently in case of early recurrence. Despite an immediate start of antiviral treatment, early recurrence has a significant negative impact on the outcome of transplantation. Orv. Hetil., 2013, 154, 1058-1066.
Orvosi Hetilap 07/2013; 154(27):1058-1066. DOI:10.1556/OH.2013.29647
[Show abstract][Hide abstract] ABSTRACT: The main indication of the Hungarian Liver Transplant Program is liver cirrhosis caused by hepatitis C.
Authors present the results of liver transplantations performed due to HCV infection.
The data (donor-, recipient-, perioperative characteristics, survival, serum titer of C RNA, histology) of 111 HCV positive recipients were evaluated, that are 37.6% of the 295 patients, who were transplanted since 1995 till the closure of this report.
Twenty-two (22) of them (20%) died in the early postoperative period, for other reasons, before the recurrence of the HCV was detectable. Among the 89 HCV-positive patients the recurrence of the HCV is still not detected in 16 cases (18%), and there is a histology-proven recurrence in 73 cases (82%). In 40 cases (56%) the viral recurrence was proven within 1 year after OLT, while in 32 cases (44%) over 1 year. The cumulative 1, 3, 5, and 10 years patient survival is 73%, 67%, 56% and 49%, among HCV-positive patients and 80%, 74%, 70% and 70% among HCV-negatives. The difference is significant. The cumulative graft survival at the same time points is 72%, 66%, 56% and 49% among HCV-positives and 76%, 72%, 68% and 68% among HCV-negatives, which is a non-significant difference. The serum titer of HCV-RNA was significantly higher among those HCV-patients who had an early viral recurrence within 1 year, compared to those who had a late one. In case of an early HCV-recurrence the Knodell-score was significantly higher in the 6 months posttransplant biopsy than that of in case of late viral recurrence, however, less fibrosis was observed in early recurrence.
An early HCV recurrence can be expected in case of an older donor, with a marginal or fatty liver graft transplanted with a higher transfusion need and having an acute rejection treated with steroid bolus in the postoperative period. The protocol of the postoperative antiviral treatment differs from the average: the so-called "stop-rule" cannot be applied, since less then 10% of the recipients are expected to turn to HCV-PCR-negative due to the immunosuppression. The combined interferon + ribavirin treatment is maintained in spite of RNA-positive state, further, a second or third course of treatment might also be applied. The prolonged and--in case if necessary--repeated antiviral treatment prevents fibrosis, and therefore rate of retransplantation need. The better is the general state of the patient the results of a secondary liver transplantation are better as well. MELD-score can help to set the exact timing for a re-OLT.
Orvosi Hetilap 11/2007; 148(42):1971-9. DOI:10.1556/OH.2007.28176
[Show abstract][Hide abstract] ABSTRACT: The authors summarize the demographic, morbidity and mortality characteristics of the Hungarian Liver Transplant Program.
They evaluate the changes and development, that has taken place with regard to indications, recipient population and characteristics, operation technique, and peroperative patient management.
In order to present the development, data are compared between two time periods (before and after 1999). The results are summarized on Tables and statistical Figures. Categorical variables are evaluated by chi2-test, continuous ones are with Levene Test (for homogeneity of means), Student T test and Mann-Whitney U-test. Cumulative survivals are computed with Kaplan-Meier log rank analysis.
194 primary liver transplantation have been performed. The hepatitis C was the leading indication from the beginning. Ten (10) liver transplantation have been performed in 1995, while 44 in 2004. The mortality within the first 2 months decreased from 24% to 5%. The 1, 3 and 5 year cumulative patient survival increased from 55%, 45% es 39% (1995-1997), to 72%, 64% es 61% (1998-2000). Recently this is 78%, 77% es 77%.
Between 1995-1997 conventional liver transplantation became standard, while piggy back turned to be popular from 1998. From 1999 the HCV-PCR monitoring, the combined antiviral treatment, the UW perfusion of the donors took place. From 2003 we introduced the tailored immunosuppression, the steroid-free protocol for viral diseases. Total infused volume was decreased together with the amount of transfusion. The retrograde graft reperfusion (from the caval side) was introduced in 2004 together with the split technique in the liver transplantation and the rebirth of the pediatric program. The overall outcome of the retrospective analysis is, that the program has been developed to European standards with respect to its volume, technical capabilities and results.
[Show abstract][Hide abstract] ABSTRACT: The authors present a case of an adult with Kawasaki syndrome, who, due to jaundice, enlarged liver and abnormal liver function tests, was admitted the hospital with the suspicion of liver disease. The symptoms of Kawasaki syndrome appeared during the first nine days of the hospital stay. The authors emphasise, that liver function tests are frequently abnormal in adults presenting with this clinical entity, therefore Kawasaki syndrome should be taken into consideration in the differential diagnosis of liver diseases.
[Show abstract][Hide abstract] ABSTRACT: Little is known about the fungal colonization of the esophagus. Since alcoholic liver disease (ALD) patients are prone to fungal esophagitis, we have investigated the esophageal fungal colonization of this patient group.
One hundred consecutive ALD patients were enrolled in this prospective study. 22 patients with dyspeptic symptoms acted as controls. After taking an oropharyngeal swab, patients underwent an upper gastrointestinal endoscopy and surface material was obtained from the esophagus for direct smears and culture.
In the ALD group pseudohyphae were found in 21.5% and yeast forms in 6.4% of the direct smears. The culture was positive in 40.8% of the ALD patients, the isolated strains were: 30 C. albicans, 2 C. kefyr, 2 C. krusei, 1 C. zeylanoides and in 3 cases the species could not be identified. 41.9% of ALD patients and 13.6% of control patients (p = 0.013) had fungi in their esophagus. Significantly more ALD patients had fungal esophagitis than in the control group (19.3% vs. 0%, p = 0.021), the rate of fungal colonization was also higher, but the difference was not significant (22.5% vs. 13.6%). A significantly higher rate of fungal esophagitis and esophageal colonization was found in patients with fungi in their oropharyngeal swabs (p = 0.00001).
Fungal colonization of the esophagus is frequent in ALD patients. Its presence might have clinical significance in the case of liver transplantation.
Zeitschrift für Gastroenterologie 11/2000; 38(10):821-5. DOI:10.1055/s-2000-10000 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Authors describe the history of a 37-year-old man suffering from multiple purulent brain abscess. The multiple brain abscess evolved primarily from a gluteal abscess to the lung, and secondarily from the lung to the brain by hematogenous spreading of the bacteria. The identification of the pathogene/s was unsuccessful despite numerous bacteriological examination. Despite many regimens of empiric antibacterial therapy the brain abscesses progressed, neurologic state of the patient deteriorated. At long last, the patient was given chloramphenicol. After that, he had no more fever, his consciousness cleared, no more epileptic convulsion occurred and the cell number of the cerebrospinal fluid became normal. The patient was thought to be cured and was sent home. Two months later fever occurred again and it was accompanied by excrutiating headache, increasing disorientation, so the patient was admitted to the hospital. The occurrence of a new brain abscess and purulent meningitis indicated the relapse of the disease. It was again unsuccessful to identify the pathogene/s therefore the authors treated the patient with many empiric antibiotic regimen, all of which-including chloramphenicol too--proved to be uneffective. As all the therapeutic regimens usually used in the treatment of purulent brain abscess were uneffective--including the combinations which have the widest antibacterial spectrum, authors gave meropenem as ultimum refugium. Some days later the fever came to an end, his consciousness cleared, the brain pressure and the cerebrospinal fluid became normal. The patient had no serious complaints in the course of the four years follow up, his residual neurologic symptoms regressed. On the base of this case history, authors suppose that meropenem--which has already proved to have a very wide antibacterial spectrum and to be very effective in the therapy of many kinds of serious bacterial infections--could also become a promising new therapeutic alternative in the treatment of purulent brain abscess.