No abstract

Acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP) are caused by mutations in the hydroxymethylbilane synthase (HMBS), protoporphyrinogen oxidase (PPOX), and coproporphyrinogen oxidase (CPOX) genes, respectively. This study aimed to identify mutations in seven Bulgarian families with AIP, six with VP, and one with HCP. A total of 33 subjects, both symptomatic (n = 21) and asymptomatic (n = 12), were included in this study. The identification of mutations was performed by direct sequencing of all the coding exons of the corresponding enzymes in the probands. The available relatives were screened for the possible mutations. A total of six different mutations in HMBS were detected in all seven families with AIP, three of which were previously described: c.76C>T [p.R26C] in exon 3, c.287C>T [p.S96F] in exon 7, and c.445C>T [p.R149X] in exon 9. The following three novel HMBS mutations were found: c.345-2A>C in intron 7-8, c.279-280insAT in exon 7, and c.887delC in exon 15. A total of three different novel mutations were identified in the PPOX gene in the VP families: c.441-442delCA in exon 5, c.917T>C [p.L306P] in exon 9, and c.1252T>C [p.C418R] in exon 12. A novel nonsense mutation, c.364G>T [p.E122X], in exon 1 of the CPOX gene was identified in the HCP family. This study, which identified mutations in Bulgarian families with AHP for the first time, established seven novel mutation sites. Seven latent carriers were also diagnosed and, therefore, were able to receive crucial counseling to prevent attacks.

No abstract

The histopathology of hepatitis B is diverse and reflects the natural history of chronic HBV-infection. Liver biopsy is gold standard for assessment of disease-activity and fibrosis. Treatment-decision is based on the assessment of liver disease severity as well as on patient's age, viral load, and HBeAg status. The relationship between these parameters and liver histopathology is not studied in details. We analysed treatment-naïve patients from single canter: 231 with histologically-proven chronic hepatitis B (CHB) and 104 subjects with clinical, laboratory and ultrasound signs of liver cirrhosis (LC). Viral load and HBV-serology were measured in all cases by real-time PCR and ELISA, respectively. Histological assessment of liver biopsies was performed according to METAVIR. Our results showed that the number of HBeAg-positive patient decreases with the increase of the disease activity from A0 to A3 as well as with the increase of the fibrosis stage from F1 to F4. In HBeAg-positive CHB patients both inflammation and fibrosis were more frequently mild or moderate. Severe disease activity (A3) and advanced fibrosis were observed more frequently in HBeAg-negative subjects. HBeAg-positive patients are younger than HBeAg-negative. Such an age difference exists into all separate subgroups