ABSTRACT
Our study includes 102 cases of liver biopsy previously diagnosed with chronic alcoholic hepatitis and also B and C viral hepatitis. In these cases, we analyzed the extension of fibrosis with two different methods. First, we evaluated fibrosis with the subjective Knodell score; secondly, we used digital image analysis to achieve this. We also used immunohistochemical methods to mark those cells positive at Smooth Muscle Actin (SMA) and Glial Fibrillary Acidic Protein (GFAP). We have observed that the extension of fibrosis was most predominant in cases with B viral chronic hepatitis, while the number of cells responsible of fibrosis (stellate cells, myofibroblasts) was highest in C viral chronic hepatitis. These differences help clinician to divide patients into those who may be treated with interferon and those treatable with antiviral therapy. We observed ductular reaction (as shown by cytokeratin 7 immunostaining) within the lobular structure more frequently in alcohol related chronic hepatitis, whilst in C viral chronic hepatitis this reaction was more readily seen in portal spaces. We have concluded that patients with C viral hepatitis can benefit most from a correctly indicated hepatic biopsy since in these cases the lesions might be observed in an early and potentially curable phase.
Subject(s)
Bile Ducts/pathology , Hepatitis B, Chronic/pathology , Hepatitis C, Chronic/pathology , Liver Cirrhosis/pathology , Liver Diseases, Alcoholic/pathology , Adult , Female , Hepatitis B, Chronic/metabolism , Hepatitis B, Chronic/virology , Hepatitis C, Chronic/metabolism , Hepatitis C, Chronic/virology , Humans , Immunohistochemistry , Liver Cirrhosis/metabolism , Liver Cirrhosis/virology , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/virology , Male , Middle AgedABSTRACT
Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19(+) peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.
