Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in patients with chronic liver disease.
To assess the value of TE for predicting the stage of ...fibrosis.
Liver biopsy and TE were performed in 150 consecutive patients with chronic hepatitis C-related hepatitis (92 men and 58 women, age 50.6 (SD 12.5) years on the same day. Necro-inflammatory activity and the degree of steatosis at biopsy were also evaluated.
The areas under the curve for the prediction of significant fibrosis (> or = F2), advanced fibrosis (> or = F3) or cirrhosis were 0.91, 0.99 and 0.98, respectively. Calculation of multilevel likelihood ratios showed that values of TE < 6 or > or = 12, < 9 or > or = 12, and < 12 or > or = 18, clearly indicated the absence or presence of significant fibrosis, advanced fibrosis, and cirrhosis, respectively. Intermediate values could not be reliably associated with the absence or presence of the target condition. The presence of inflammation significantly affected TE measurements in patients who did not have cirrhosis (p<0.0001), even after adjusting for the stage of fibrosis. Importantly, TE measurements were not influenced by the degree of steatosis.
TE is more suitable for the identification of patients with advanced fibrosis than of those with cirrhosis or significant fibrosis. In patients in whom likelihood ratios are not optimal and do not provide a reliable indication of the disease stage, liver biopsy should be considered when clinically indicated. Necro-inflammatory activity, but not steatosis, strongly and independently influences TE measurement in patients who do not have cirrhosis.
Summary
Background
Cryoglobulinaemic vasculitis (CV) is a lymphoproliferative disorder related to hepatitis C virus (HCV) infection; anti‐viral therapy is the first therapeutic option. CV can be ...incapacitating, compromising the patients’ quality of life (QoL). In a controlled study, interferon‐based therapy was associated with a lower virological response in vasculitic patients than in patients without vasculitis. Limited, uncontrolled data on direct‐acting anti‐virals are available.
Aim
To evaluate safety, clinical efficacy, virological response and the impact of interferon‐free treatment on QoL in HCV patients with and without mixed cryoglobulinaemia (MC).
Methods
We prospectively studied HCV patients with cryoglobulinaemia (with vasculitis‐CV‐ and without vasculitis‐MC‐) and without cryoglobulinaemia (controls), treated with direct‐acting anti‐virals. Hepato‐virological parameters, CV clinical response and impact on QoL were assessed.
Results
One hundred and eighty‐two HCV patients were recruited (85 with CV, 54 with MC and 43 controls). A sustained virological response at 12 weeks (SVR12) was achieved in 166 (91.2%) patients (77/85 CV, 48/54 MC, 41/43 controls). In CV SVR patients, cryocrit levels progressively decreased and clinical response progressively improved, reaching 96.7%, 24 weeks after treatment. QoL, baseline physical and mental component summaries were lower in the CV group compared to the other groups (P < 0.05). Scores improved in all groups, and significantly in CV patients after SVR.
Conclusions
No significant differences in SVR rates were recorded between cryoglobulinaemic patients and controls and a high clinical and immunological efficacy was confirmed in CV, supporting the role of interferon‐free therapy as the first therapeutic option. Interestingly, CV patients had worse baseline QoL than other HCV‐positive groups and interferon‐free therapy was effective in significantly increasing QoL, suggesting the important role of direct‐acting anti‐viral‐based therapy in improving CV's individual and social burden.
Five children were diagnosed with congenital dacryocystocele; in all cases, the cystic lesion was unilateral; age ranged from 7 to 60 days (mean 29 days). The mean ultrasonography diameter of the ...cyst, at the time of the diagnosis, was 11.51 mm. Topical and systemic antibiotics and massage were prescribed. One patient had no recurrence of the dacryocystocele but 4 showed no improvement with medical treatment; they were submitted to successful probing in the first months of life under general anaesthesia. Nasal endoscopy revealed a nasolacrimal cyst in one patient. True dacryocystocele is relatively rare: ultrasound is a simple, non-invasive method that can reliably distinguish dacryocystocele from other pathological conditions. Several reports have described a variable natural course of these lesions but there are controversial opinions regarding their management. Initially, we treated this congenital anomaly with digital massage, and topical and systemic antibiotics. Probing under general anaesthesia was performed in the event of dacryocystitis or lack of resolution after a short trial period with digital massage. Particular attention was paid to nasal bilateral endoscopy to exclude a nasal obstruction caused by cystic swelling of the nasolacrimal duct. When performed, the probing procedure was successful in all patients.
Summary
HCV‐related mixed cryoglobulinemia (MC) is characterized by clonal expansion of B cells producing a polyreactive natural antibody (rheumatoid factor) and interferon (IFN)‐based therapy is the ...first therapeutic option in mild‐moderate MC. Single nucleotide polymorphisms (SNPs) proximal to genes involved in the innate response (IL28B/IFN‐λ gene family) are strongly associated with spontaneous and IFN‐induced viral clearance in hepatitis C, but no data exist about their role in HCV‐positive MC. A large cohort of patients with HCV and MC was studied to evaluate the influence of IL28B genotype on the response to treatment and/or the evolution to MC of HCV infection. The rs12979860/rs8099917 IL28B polymorphisms were analysed in 481 consecutive HCV‐positive subjects (250 with MC and 231 without MC, as controls) using real‐time PCR and direct sequencing. Hundred and fifteen HCV patients with MC received standard anti‐HCV therapy, and the results were evaluated according to the IL28B SNP distribution. Similar IL28B SNPs allele frequencies were recorded for patients and controls. IL28B major allele homozygosis (for both SNPs tested) was tightly correlated with virological and clinical response (P = 0.002). A statistically significant association was limited to ‘difficult‐to‐treat’ (G1/4) HCV genotypes. The IL28B genotype was a strong independent predictor of response (P = 0.007, OR 6.06; CI 1.65–22.22). The IL28B genotype was confirmed to be a useful predictor of response to IFN‐based therapy in patients with HCV and MC. The very close correlation between IL28B SNP distribution, virological and clinical response definitively confirmed the key role played by HCV in MC. Conversely, the IL28B genotype does not seem to influence the evolution to MC.
Monocyte chemotactic protein (MCP)-1 is a chemoattractant and activator for circulating monocytes and T lymphocytes. We investigated MCP-1 protein and gene expression during chronic liver disease at ...different stages, using immunohistochemistry and in situ hybridization, respectively. In normal liver, a modest expression of MCP-1 was confined to few peri-sinusoidal cells and to bile duct epithelial cells. During chronic hepatitis, MCP-1 immunostaining and gene expression were evident in the inflammatory infiltrate of the portal tract. In tissue from patients with active cirrhosis, MCP-1 expression was clearly up-regulated and was present in the portal tract, in the epithelial cells of regenerating bile ducts, and in the active septa surrounding regenerating nodules. A combination of in situ hybridization for MCP-1 and immunohistochemistry showed that activated stellate cells and monocyte/macrophages contribute to MCP-1 expression in vivo together with bile duct epithelial cells. Comparison of serial sections of liver biopsies from patients with various degrees of necro-inflammatory activity showed that infiltration of the portal tracts with monocytes/macrophages is directly correlated with the expression of MCP-1. These data expand previous in vitro studies showing that secretion of MCP-1 may contribute to the formation and maintenance of the inflammatory infiltrate observed during chronic liver disease.
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