Association between genetic mutations and the development of autoimmune thyroiditis in patients with chronic hepatitis C treated with interferon alpha.

BACKGROUND: Considerable progress was made by the introduction of interferon to the treatment of chronic hepatitis C virus infection. This treatment, however, is associated with the risk of developing or exacerbating autoimmune diseases, with chronic autoimmune thyroiditis being one of them. The aim of our study was to evaluate the predisposition to autoimmune thyroiditis in patients with chronic hepatitis C virus during IFN-alpha therapy, depending on the presence of polymorphisms in the promoter region of CTLA-4C (-318)T gene and in exon 1 of A49G gene as well as C1858T transition of PTPN22 gene. METHODS: The study was conducted in 149 patients aged between 18 and 70 years (mean of 43.9 years), including 82 men and 67 women. Control group for the assessment of the distribution of analyzed polymorphism of genotypes consisted of 200 neonates, from whom umbilical blood was drawn for the tests. The patients were divided into three groups: group 1 consisted of 114 patients without thyroid impairment before and during IFN-alpha therapy, group 2 contained 9 patients with AT with the onset prior to IFN-alpha treatment, and group 3 comprised 26 patients with AT starting after the beginning of IFN-alpha therapy. RESULTS: The frequency of C1858Tand C(-318)T genotypes observed in the study group did not differ significantly from control group. A significant difference, however, was found for A49G polymorphism. CONCLUSIONS: No association was demonstrated between the occurrence of autoimmune thyroiditis with the onset during IFN-alpha therapy and the presence of polymorphisms within CTLA-4 C(-318)T gene in the promoter region and A49G in exon 1, as well as C1858T transition of PTPN22 gene.

The influence of interferon alpha on the induction of autoimmune thyroiditis in patients treated for chronic viral hepatitis type C.

BACKGROUND: Different forms of interferon alpha (IFN-α) have been used for several years in the treatment of chronic viral hepatitis type C (CVHC). Currently, pegylated forms of interferon alpha (PegIFN-α) in combination with ribavirin is the standard treatment. During therapy with IFN-α, side-effects occur, including thyroid diseases. The aim of this study was an evaluation of administered interferon's impact on the frequency of autoimmune thyroiditis (ATI) occurrence among patients with CVH type C treated with INF-α and an assessment as to whether the type of interferon used is significant in ATI development. MATERIAL AND METHODS: 149 patients aged 18-70 (mean 43.9 ± 2.3 years) with CVH type C participated in the study. The serum concentrations of thyrotrophin (TSH), free tyrosine (FT4), triiodothyronine (FT3), thyreoglobulin (Tg), antithyroid antibodies: antiperoxidase (TPOAb) and antithyreoglobulin (TgAb) were evaluated before, and after six and 12 months of treatment. Additionally, the thyroid echostructure was evaluated with ultrasonography. Sixty out of 149 patients received Peg-INF-α, and 89 patients were treated with recombinant IFN-α. RESULTS: ATI was confirmed in nine patients (6.04%) with CVH type C before the introduction of interferon. Seven of them underwent an exacerbation of hypothyroidsm during therapy with interferon. In 24 patients (17.14%), who did not have the signs of ATI at baseline, an elevated concentration of antithyroid antibodies was detected during therapy with interferon. The mean concentrations of TPOAb before, and after six and 12 months of treatment were, respectively: 12.4; 310.4 and 141.3 IU/ml, and the mean concentrations of TgAb were, respectively: 17.40; 108.0; and 125.6 IU/ml. After six months of treatment in this group of patients, 11 had hypothyroidsm and six had hyperthyroidsm. After 12 months of therapy, four patients had hypertthyroidsm and four showed signs and symptoms of hypothyroidsm; the remaining patients were in a euthyroid state. In ultrasound examination, reduction of echogenicity among patients with ATI before treatment was revealed in 75% of cases at baseline, in 83.3% after six months and in 100% after 12 months of treatment. In the group of patients presenting with ATI during IFN-α therapy, in which no disorders were found in initial examination, after six months of treatment a reduction of echogenicity was found in 69.2%, and after 12 months in 75%, of patients. CONCLUSIONS: Among patients treated with interferon due to CVH type C, there is a risk of the development of ATI or the exacerbation of an existing one. There is no significant difference in ATI presentation in relation to the type of IFN-α used for treatment.

[Efficacy of combination therapy with interferon-alpha and ribavirin for chronic hepatitis C in relation to liver fibrosis and serum aminotransferase activity]. / Skutecznosc skojarzonego leczenia interferonem z rybawiryna przewleklego wirusowego zapalenia watroby typu C zaleznie od stopnia wloknienia oraz aktywnosci enzymów watrobowych.

The aim of the study was to evaluate the efficacy of interferon alpha (IFNalpha)-2b in combination with oral ribavirin for treatment of chronic hepatitis C in relation to age, sex, liver enzymes activity as well as to grading and staging of liver disease in histologic examination. There were 154 adult patients assigned for the retrospective analysis including 69 females and 85 males of 16 to 70 years of age (mean age 43.3 +/- 12 years) treated with IFNalpha and ribavirin for 24 or 48 weeks. Sustained virological response was achieved in 66 patients (42.9%) and sustained biochemical response rate was 44%. Sustained response correlated with younger age, lower baseline AST, GT and ALP activities as well as with lower staging of liver disease. Combination treatment with interferon and ribavirin was significantly more effective in patient under 40 years of age and in patients without cirrhosis. Sex, baseline ALT activity and histological grading of liver disease did not differ between sustained responders and non-responders. Sustained virological response on combination therapy was achieved in 5 out of 7 previous monotherapy relapsers (71.4%) whereas only 5 patients out of 22 monotherapy non-responders benefited from combination therapy (22.7%). In conclusion, efficacy of combination therapy with IFNalpha and ribavirin in patients with liver cirrhosis is less effective and should be considered in chosen situations, especially in younger patients. Normal ALT activity should not be an exclusion criterion to therapy. Combination retherapy in previous monotherapy non-responders seems to be ineffective whereas in monotherapy relapsers good sustained response can be achieved.

Hepatitis B core antigen in liver tissue from HBs-positive, HBe-negative patients.

BACKGROUND/AIMS: We aimed to study the relationship between HBcAg in liver tissue, histological and biochemical activity and serum HBV-DNA levels among HBeAg-negative patients. METHODOLOGY: 49 biopsy specimens taken from 16 females and 29 males were studied. Immunostaining for HBcAg was performed with commercially available kits (Dako). Serum HBV-DNA was detected by the hybridization method, in case of negative hybridization, repeated by PCR. RESULTS: HBcAg was found in 16 biopsy specimens (32.6%) (group I)--in 10 cases in hepatocytes nuclei and cytoplasm, in 5 in the nuclei and in one case in cytoplasm only. 15 out of 16 patients were serum HBV-DNA positive. Seven patients showed chronic liver disease of moderate or severe activity with HBcAg expression both in the nuclei and cytoplasm. Group II consisted of 33 patients who were HBcAg-negative. In 7 patients HBV-DNA was not found by hybridization or by PCR. In eleven patients ALT and AST activity exceeded 1.5x the ULN. ALT and AST differed significantly between group II and I. CONCLUSIONS: In our opinion immunohistochemical examination is an essential part of classification to antiviral treatment. HBcAg immunostaining should be performed in every HBeAg-negative patient to exclude reasons for aminotransferase elevation other than HBV infection.

[Relationship of serum alanine aminotransferase (ALT) to body weight, age and sex in blood donors population]. / Aktywnosc aminotransferazy alaninowej (ALT) a masa ciala, wiek i plec w populacji krwiodawców.

The activity of alanine aminotransferase (ALT) is the most popular parameter in hepatology. Increase of ALT usually suggests the damage of hepatocytes. The aim of the study was to assess the range of value of serum alanine aminotransferase in healthy population and to assess the relationship between ALT level and body mass index (BMI), age and gender. We have analyzed a large population of healthy blood donors--all of them were screened for ALT, weight and height. Patients were divided into four groups: I--patients with underweight, II--patients with normal weight, III--patients with overweight, IV--obese patients. In the studied population 862 persons were taken into account (820 men and 42 women), 19-62 years of age. The ALT level varied from 6 to 77 U/L, mean 27.39 U/L. Inadequate BMI was found in 12 persons, normal BMI in 497 persons, overweight in 270 persons and obesity in 83 persons. ALT and BMI are statistically significantly higher in men than in women. In general population and in men group we found correlations between ALT and BMI (p = 0.0000), between ALT and age (p = 0.0000). In women we did not find those dependences. ALT level was statistically significantly higher in groups with higher BMI: ALT level in group II was higher than in group I (p < 0.024), ALT level in group III was higher than in group III (p = 0.0000). We did not find any differences in ALT level between group III and IV. ALT level strongly correlates with body mass, age and gender. We suggest the necessity of taking into consideration those parameters in a clinical interpretation of ALT level.

Terlipressin inhibits in vivo aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis.

In cirrhosis, lipopolysaccharide (LPS, a product of Gram-negative bacteria) in the blood may cause septic shock. LPS-elicited induction of arterial inducible nitric oxide synthase (iNOS) results in nitric oxide (NO)-induced vasodilation, which causes arterial hypotension and hyporeactivity to alpha(1)-adrenergic constrictors. In vitro studies have suggested that vasopressin inhibits iNOS expression in cultured vascular smooth muscle cells exposed to LPS. Thus, the aim of this study was to investigate the effects of terlipressin administration (a vasopressin analog) on in vivo LPS-induced aortic iNOS in rats with cirrhosis. LPS (1 mg/kg, intravenously) was administered followed by the intravenous administration of terlipressin (0.05 mg/kg, intravenously) or placebo 1 hour later. Arterial pressure was measured, and contractions to phenylephrine (an alpha(1)-adrenoceptor agonist), iNOS activity, and iNOS expressions (mRNA and protein) were investigated in isolated aortas. LPS-induced arterial hypotension and aortic hyporeactivity to phenylephrine were abolished in rats that received terlipressin. LPS-induced aortic iNOS activity and expression were suppressed in terlipressin-treated rats. In conclusion, in LPS-challenged rats with cirrhosis, terlipressin administration inhibits in vivo LPS-induced aortic iNOS expression. Terlipressin administration may be a novel approach for the treatment of arterial hypotension and hyporeactivity to alpha(1)-adrenergic constrictors in patients with cirrhosis and septic shock.