Noninvasive diagnosis of liver fibrosis: utility of data mining of both ultrasound elastography and serological findings to construct a decision tree.

OBJECTIVE: Although liver biopsy is the gold standard for viral liver disease management, it is invasive and the sampling error rate is problematic. Real-time tissue elastography (RTE), a recently developed method of ultrasound elastography, can be used to assess liver fibrosis noninvasively but the overlap between fibrosis stages limits its ability to assess liver fibrosis adequately when used alone. METHODS: A multicenter collaborative study involving 542 patients with chronic viral hepatitis and cirrhosis who were scheduled to undergo liver biopsy compared the image features obtained from RTE image analysis, the liver fibrosis index (LFI), and pathological diagnosis. RTE and a blood test were performed on the same day as the liver biopsy. Data mining was also performed to construct a decision tree, and its diagnostic performance for assessing liver fibrosis was evaluated. RESULTS: The LFI was higher in patients with chronic hepatitis C (CHC) than in those with chronic hepatitis B (CHB). When a decision tree was constructed by data mining of RTE and serological findings, the diagnostic accuracy was very high for all fibrosis stages, with respective rates at F1, F2, F3, and F4 of 94.4, 54.1, 38.7, and 81.3% for patients with CHC and of 97.1, 50.0, 43.8, and 80.6% for patients with CHB. CONCLUSIONS: The variation in LFI values between the different etiologies appears to reflect the difference in the development style of liver fibrosis. The decision tree for assessing liver fibrosis constructed by data mining of both RTE and serological findings had a high diagnostic performance in assessing liver fibrosis and shows promising clinical utility.

Non-invasive evaluation of hepatic fibrosis for type C chronic hepatitis.

OBJECTIVE: The aim of this study was to investigate liver fibrosis using non-invasive Real-time Tissue Elastography (RTE) and transient elastography (FibroScan) methods. METHODS: RTE, FibroScan and percutaneous liver biopsy were all performed on patients with chronic liver disease, particularly hepatitis C, to investigate liver fibrosis. RESULTS: FibroScan and RTE were compared for fibrous liver staging (F stage), which was pathologically classified using liver biopsy. In FibroScan, significant differences were observed between F1/F3 and F2/F4, but no such differences were observed between F1/F2, F2/F3 and F3/F4. In RTE, significant differences were observed between F1/F2, F2/F3 and F2/F4. But for F3/F4, no significant differences were observed. CONCLUSION: FibroScan and RTE correlated well with F staging of the liver. In particular RTE was more successful than FibroScan in diagnosing the degree of liver fibrosis.

The induction of dentin bridge-like structures by constructs of subcultured dental pulp-derived cells and porous HA/TCP in porcine teeth.

The purpose of this study was to investigate dentin-bridge formation in teeth following the transplantation of dental pulp-derived cells seeded on hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds. The dental pulp tissues were removed from the extracted first molar teeth of miniature pigs and single cell populations were subcultured. Second-passage cells that had alkaline phosphatase activity were combined with scaffolds. Cell-scaffold constructs were placed in contact with the exposed pulp tissue. The dimensions of the exposed pulp site were approximately 1-2.5 mm in diameter and 2-3 mm in depth from the tooth surface. After placing the constructs, the tooth was restored with composite resin. Six weeks after transplantation, hard tissue formation was observed on the pulp tissue in histology. Dentinal tubule-like structures were observed in most of the hard tissue generated, and columnar cells, which showed positive immunoreactions with dentin sialoprotein (DSP) and heat shock protein (HSP)-25, were aligned beneath the hard tissues. When only scaffolds were placed on the pulp tissues, particles of hard tissue were formed, however dentinal tubule-like structures and odontoblasts were not observed despite the formation of hard tissue. In conclusion, the implantation of dental pulp constructs into pulp exposed stimulates the formation of calcified dentin-like structures.

Differential effect of scaffold shape on dentin regeneration.

The effect of scaffold shape on dentin regeneration is not well understood. In this study, porous hydroxyapatite/beta-tricalcium phosphate (HAp/beta-TCP), powdered HAp/beta-TCP, and polyglycolic acid (PGA) fiber mesh were used as scaffolds and transplanted with cultured porcine dental pulp-derived cells into the backs of nude mice. Samples were harvested after 6 weeks. Newly-formed hard tissue was observed in all transplants. When porous HAp/beta-TCP was used, dentin-like hard tissue was observed on the inner wall with minimum cell inclusions and odontoblast-like cells were aligned adjacent to the hard tissue. When HAp/beta-TCP powders or PGA were used, bone-like hard tissues showed cell inclusions and cell alignment was not observed. Hard tissue from the HAp/beta-TCP block group was positive for type I collagen, osteonectin, bone sialoprotein and dentin sialoprotein (DSP), which are markers for dentin. This result was confirmed by in situ hybridization with a dsp probe. Only the aligned cells were positive with an antisense probe. On the other hand, hard tissue from other scaffolds showed incomplete expression of both bone and dentin markers and they were negative for osteonectin and DSP. These results suggest that scaffold shape affects the type of tissue regenerated by dental pulp-derived cells.

Differential inducibility of human and porcine dental pulp-derived cells into odontoblasts.

A robust method for generating odontoblasts from cultured dental pulp cells has not been established. In this study, efficient methods for deriving odontoblasts from cultured human and porcine dental pulp-derived cells were investigated with special attention to species differences. Cultured human cells showed relatively low alkaline phosphatase (ALP) activity in the presence of dexamethasone (Dex) and beta-glycerophosphate (beta-Gly). In contrast, the addition of 1,25-dihydroxyvitaminD(3) (VitD3) significantly increased the ALP activity. In porcine cells, beta-Gly alone or a combination of Dex and beta-Gly significantly increased ALP activity; however, addition of VitD3 reduced this activity. RT-PCR and Western blotting analysis revealed that the combination of three induction reagents on human cells significantly upregulates the expression of osteocalcin mRNA, and dentin sialoprotein. We propose that the combination of Dex, beta-Gly, and VitD3 is critical for differentiation of human dental pulp-derived cells into odontoblasts. In addition, the inducibility of dental pulp-derived cells presented remarkable species differences.