Conventional management of Interferon-α-Induced Hyperthyroidism (IIH) with radioactive iodine (RAI) may be used when treatment with beta blockers or antithyroid drugs (ATD), proves ineffective or is contraindicated.We present a 38-year-old woman who has been treated with combined pegylated interferon alpha (INF-α) and Ribavirin for chronic hepatitis C. Destructive thyrotoxicosis appeared after four months of continuous IFN-α therapy and a beta blocker was prescribed. Initially, the patient presented normal TSH 2.4 µIU/mL, however during therapy with INF-α, TSH diminished to 0.05 and thyroid hormones were elevated: fT4 23.1 pmol/L, fT3 7.2 pmol/L. Ultrasound examination showed completely irregular and greatly decreased echogenicity of the thyroid gland. The radioiodine uptake (RAIU) was deeply decreased to 2 and 3% at 5 h and 24 h, respectively. The thyroid scintiscan showed lack of isotope accumulation. Hypothyroidism developed and L-thyroxine was prescribed. The following year, hyperthyroidism reoccurred with TSH 0.08 µIU/mL, fT4 26.4 pmol/L, fT3 8.2 pmol/L, positive TSHR-Abs 6.2 (normal <2 IU/L) and mild Graves' Ophthalmopathy (GO). RAIU values were 23% at 5 h and 46% at 24 h. Thyroid scintiscan showed diffuse goiter. At this point beta blocker was introduced and ATD was started. After three months of therapy an increased level of aminotransferases and granulocytopaenia were observed. Hence, the patient received RAI and glucocorticosteroid, while INF-α therapy was continued. After approximately 4 months, hypothyroidism reappeared with insignificantly raised TSH level. One year later the patient was euthyroid and required no further treatment.Our report suggests that: 1. Radioiodine therapy might be an effective and safe method of treatment in cases of IIH with mild GO. 2. IFN-α therapy need not be discontinued in patients with IIH.
To evaluate the association of IFNL3 (IL28B) SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis C (CHC).The study enrolled 196 CHC Polish patients (82 women and 114 men in age 20-64) infected with hepatitis C virus (HCV) genotype 1. They were treatment naïve and qualified to pegylated interferon alpha (PEG-IFN-α) and ribavirin (RBV) therapy. The analyzed baseline parameters included: degree of inflammation, stage of fibrosis, viral load as well as alanine aminotransferase (ALT), asparagine aminotransferase (AST) and total bilirubin (TBIL). The analysis of response to therapy included: sustained virological response (SVR), defined as undetectable serum HCV RNA level six month after completion of 48-wk therapy, and relapse, defined as achieving undetectable viral load at the end of treatment but not SVR. HCV genotyping and HCV RNA quantification were performed using commercially available tests. DNA was isolated from peripheral blood mononuclear cells or from buccal cell swabs. In addition to rs4803217, also single nucleotide polymorphisms (SNPs) (rs12979860, rs8099917 and rs12980275) of known significance in predicting of HCV clearance were analyzed. SNPs were determined by high resolution melt analysis and confirmed by sequencing of amplicons.Frequency of rs4803217 genotypes in studied group was as follows: 27.55%; 54.59% and 17.86% for CC, CA and AA, respectively. The rs4803217 SNP, similar to other analyzed SNPs, was not associated with severity of CHC (grade of inflammation, stage of fibrosis, baseline viral load as well as biochemical parameters: ALT, AST, TBIL). It was demonstrated that the rs4803217C allele is associated with SVR (C vs A: P < 0.0001; dose of C allele: P = 0.0002) and non-relapse (C vs A: P = 0.001; dose of C allele: P = 0.002). Moreover, it was found that patients with CC genotype have significantly higher response rates as compared with CA/AA patients (P < 0.0001), whereas patients carrying A allele are significantly predisposed to relapse after treatment (P = 0.0007). Moreover, the association of rs4803217 with SVR was comparable to that of rs12979860 and stronger as observed for rs12980275 and rs8099917. Association of rs4803217 with relapse, was the strongest as compared with the other SNPs. The analysis of combined rs4803217 and rs8099917 genotypes demonstrated that additional genotyping of rs8099917 had no significant impact on the prediction of SVR. Multivariate analysis revealed that among analyzed SNPs only rs4803217 is an independent predictor of SVR (P = 0.016) and relapse (P = 0.024).The rs4803217 SNP is a strong, independent and superior predictor of SVR and relapse in HCV genotype 1 infected CHC patients treated with PEG-IFN-α and RBV.
It is suggested that the tumor suppressor p53 gene, classified as an interferon-stimulated gene, is implicated in the interferon (IFN)-mediated innate immunity against viruses. This study aimed to examine the transcriptional response of the p53 gene to hepatitis C virus (HCV) infection and IFN-based therapy in chronic hepatitis C (CHC) patients. The study included 65 CHC patients (HCV genotype 1), treated with pegylated IFN-α and ribavirin, and 51 healthy individuals. p53 gene expression was quantified by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Analyses were performed before and at weeks 4 and 12 of treatment. p53 gene expression was significantly upregulated in CHC patients compared with healthy controls and at week 4 of therapy. No significant differences in p53 mRNA expression between rapid virologic responders, complete early virologic responders, and nonresponders were observed. No significant correlation was found between p53 gene expression and viral load. The results obtained indicate that HCV infection and IFN-based treatment induces p53 gene transcription in PBMCs. The p53 gene may therefore play a role in HCV infection but is not directly involved in treatment-induced HCV elimination. Moreover, variations in p53 gene expression do not determine on-treatment response in patients with chronic HCV genotype 1 infection.
Hepatitis C virus (HCV) infection in Poland affects approximately 750 thousand persons. The prevention of cirrhosis and hepatocellular carcinoma, of which approximately 20% of patients with chronic hepatitis C virus are at risk, aims at eradication of the virus by applying antiviral treatment with pegylated interferon alpha with ribavirin.In this paper the results of the standard treatment of chronic hepatitis C in a population of 169 adult patients in whom it was started in the period of 01.01.2007-30.06.2008 are analyzed. Moreover, the influence of various clinical, biochemical and viral factors on achieving therapeutic success in the form of the sustained virological response (SVR) was studied.In the group of 128 patients who received the full course of antiviral treatment, the SVR was achieved by 67.2% of patients (86 persons), whereas regarding all 169 patients who started the therapy, the sustained disappearance of viremia was found in 53.2% of patients (90 persons). Regarding 155 persons in whom the treatment was not interrupted for reasons others than virology, this value was 55.5%. For the sustained disappearance of viremia the following was favorable: genotype 3 virus, age under 40 years, body mass up to 75 kg, correct value of body mass index (BMI), low gamma-glutamyl transpeptidase (GGTP) activity before the treatment, minimum advancement of liver fibrosis in a liver biopsy (S1), complete early biochemical response (cEBR), and moreover, the achievement of negation of viremia after 12 weeks of the treatment in a group of patients infected with genotype 1 (complete early virological response, cEVR). These factors were strongly correlated with each other and that is why an analysis by the method of logistic multiple regression was impossible. Adverse reactions to the treatment and other health problems were the reasons for earlier discontinuation of the standard therapeutic scheme in 14 patients, whereby the lack of an SVR occurred in 10 of them (71.5% which is 5.9% of the studied population).
Hepatitis C virus (HCV) genotype has been described as an independent predictor of the response to therapy. A mixed infection with two types of HCV is probably an uncommon event. The aim of this study was to determine the occurrence of mixed infection with two different HCV genotypes in adult patients with chronic hepatitis C eligible for treatment.Plasma samples and clinical and demographic data were collected from 1159 patients with hepatitis C. The INNO-LiPA HCV assay was used to identify the HCV genotypes.The dominant genotype was genotype 1, which was found to be responsible for 83.9% of infections, with subtype 1b being the most common. A mixed genotype infection was detected in 26 patients (2.2%). The most common mixed genotype was 1a+1b detected in 17/26 patients (65%). Antiviral therapy led to complete elimination of both genotypes in 50% of patients with 1b+3a infection and in 33% of patients with 1b+4a infection.The results obtained showed that infection with mixed HCV genotypes in Polish patients with hepatitis C is uncommon. The selective elimination of genotypes 3a and 4a after therapy confirms the greater resistance to treatment of genotype 1b. In the context of new anti-HCV drug development, further investigations are needed to determine the clinical importance of mixed HCV infection.
Background. The prognosis concerning the treatment of patients with chronic hepatitis C (CHC) is closely related to the genotype of the virus as well as to the factors dependent on the patient. It was proved that polymorphisms of the gene encoding interleukin 28B (IL28B) are associated with sustained viral response, which in the case of profitable variants of IL28B polymorphisms may reach up to 87% of the patients.Objectives. The aim of the study is to determine the prevalence of alleles and distribution of IL28B polymorphisms genotypes in the examined group of patients with CHC in Wielkopolska Province.Material and Methods. A total of 710 people with diagnosed hepatitis C virus were examined in order to determine the distribution of polymorphisms of gene IL28B rs12979860, rs8099917 and rs12980275. The polymorphisms were evaluated by sequencing of PCR products.Results. The most often noted profitable variant was genotype TT for polymorphism rs8099917 present in 43.5% of the patients, next was AA rs12980275 in 22.5%. The rarest was the profitable variant CC of the polymorphism rs12979860 present in 17.5% of the patients. An occurrence of at least 2 IL28B polymorphisms in the preferred variants (homozygote CC, TT, AA) was found in 239 out of 710 (34%) patients, among which 117 patients had favorable genotypes for all 3 examined polymorphisms.Conclusion. The SNP distribution of gene IL28 with fixed prognostic value in the population of patients with chronic hepatitis C is different from the general population, and shows the need to evaluate polymorphisms prior to treatment.
Delayed cutaneous hypersensitivity was assessed in 120 patients (among them 109 HBsAg positive), with chronic persistent hepatitis, chronic active hepatitis, and compensated as well as decompensated liver cirrhosis by simultaneous application of seven standardized antigens and negative control ("Multitest CMI"). In 21 patients, after 12-24 months the tests were repeated. The sum of indurations of all positive responses ("score") were calculated. Responsiveness measured as results below a normal values was related to the advancing of liver disease (from 13% in chronic persistent hepatitis up to 77% in compensated and 61% in decompensated liver cirrhosis). A comparative analysis (t-Student test) of the arithmetical means of the "scores" revealed statistically significant differences between results obtained in diagnostic groups. It was also dependent from the severity of liver disease. Patients with chronic persistent hepatitis (without specific treatment) and patients with chronic active hepatitis (treated using thymus extract, TFX - "Polfa") has showed an increased "score" values. In contrast to this group, all persons with liver cirrhosis without skin-responsiveness in the first and second tests (anergy) died at the period of 18 months. "Multitest CMI" can be of value in assessing of results of immunotherapy, as well as prognosis of the course of advanced liver disease.
