Prediction of hepatic necroinflammatory activity in patients with chronic hepatitis B by a simple noninvasive model.

BACKGROUND: A model was constructed using clinical and serum variables to discriminate between chronic hepatitis B (CHB) patients with and without significant necroinflammatory activity (score 4-18 vs. score 0-3). METHODS: Consecutive CHB patients who underwent liver biopsy were divided into two sequential groups: a training group (n = 401) and a validation group (n = 401). Multivariate analysis identified alanine aminotransferase, γ-glutamyltransferase, prothrombin time and albumin as independent predictors of necroinflammatory activity. RESULTS: The area under the receiver operating characteristic curve was 0.826 for the training group and 0.847 for the validation group. Using a cut-off score of H ≤ 0.375, significant necroinflammatory activity (score 4-18) was excluded with high accuracy [78.2% negative predictive value (NPV), 72% positive predictive value (PPV), and 90.8% sensitivity] in 238 (59.4%) of 401 patients in the training group and with the same certainty (88.1% NPV, 61.2% PPV, and 95.1% sensitivity) among 204 (50.9%) of 401 patients in the validation group. Similarly, applying a cut-off score of H > 0.720, significant necroinflammatory activity was correctly identified with high accuracy (90.8% PPV, 57.7% NPV, and 92.0% specificity) in 150 (37.4%) of 401 patients in the training group and with the same certainty (91.8% PPV, 64.6% NPV, and 95.4% specificity) in 188 (46.9%) of 401 patients in the validation group. CONCLUSIONS: A predictive model based on easily accessible variables identified CHB patients with and without significant necroinflammatory activity with a high degree of accuracy. This model may decrease the need for liver biopsy for necroinflammatory activity grading in 72.1% of CHB patients.

Activated Schwann cells and increased inflammatory cytokines IL-1ß, IL-6, and TNF-α in patients' sural nerve are lack of tight relationship with specific sensory disturbances in Parkinson's disease.

AIMS: Neuroinflammation is one of the most important processes in the pathogenesis of Parkinson's disease (PD). Sensory disturbances are common in patients with PD, but the underlying pathophysiological mechanisms remain unknown. This study aimed to characterize the activation of Schwann cells (SCs) and the increase of expression of inflammatory cytokines IL-1ß, IL-6, and TNF-α in the sural nerve of PD, and further explore whether peripheral nerve inflammation is the cause of PD sensory disturbances. METHODS: A total of 14 patients with PD (including 5 with sensory disturbances and 9 without sensory disturbances) and 6 controls were included. The excitation and conduction function of sural nerve was detected by sural nerve electrophysiological examination. With sural nerve biopsy samples, ultrastructural changes of sural nerve were observed by electron microscopy; Schwann cell biomarker glial fibrillary acid protein (GFAP) and inflammatory cytokines including interleukin-1beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were detected by immunohistochemistry, and the outcome of immunostaining slice was semiquantitatively counted; double immunofluorescence was used to identify the locus immunoreactive for inflammatory cytokines. RESULTS: Compared with healthy controls, nerve conduction velocity (NCV) slowed down and sensory nerve action potential (SNAP) amplitude decreased in PD patients, accompanied by axonal degeneration and demyelinating lesions, and expression of GFAP and inflammatory cytokines was increased. Inflammatory cytokines were significantly colocalized with GFAP and slightly colocalized with NF. These indicators did not differ significantly between PD patients with and without sensory disturbances. CONCLUSION: Our study results suggest that peripheral sensory nerve injury exists in PD patients, accompanied by Schwann cell activation and inflammation, thus demonstrate peripheral nerve inflammation participates in the pathophysiological process of PD but it is not necessarily related to the patient's sensory disturbance.

Phosphorylated α-synuclein deposits in sural nerve deriving from Schwann cells: A biomarker for Parkinson's disease.

INTRODUCTION: Paresthesia is common in Parkinson's disease (PD) patients. We assumed that peripheral nerve might be implicated. This study aimed to investigate whether phosphorylated α-synuclein (pSNCA) pathology occurred in sural nerve fibers and to explore the underlying pathogenesis of paresthesia of lower limbs associated with PD. METHODS: Clinical assessments and sural nerve biopsy were performed to evaluate clinical characteristics and the deposition of total α-synuclein (tSNCA) and pSNCA in biopsy pieces using immunochemistry methods on 16 PD patients and 15 controls. In addition, immunofluorescence staining was performed using certain antibodies to characterize the component of sural nerve and to localize the expression of pSNCA. RESULTS: Deposition of pSNCA was found in 16/16 PD patients with a high positive percentage of 100% but in 0/15 controls, however, all biopsy pieces showed positive response to tSNCA immunohistological staining in nerve fibers. pSNCA was expressed mainly in Schwann cells but scarcely in axons, demonstrating a novel pattern of pSNCA expression in peripheral nervous system. CONCLUSION: Our findings suggest that peripheral somatic sensory nerve is also involved in SNCA pathology in PD. The search for pSNCA in sural nerve might serve as a novel biomarker for early diagnosis of PD and pSNCA in sural nerve may derive from Schwann cells rather than propagate retrograde along the primary sensory neurons from the central nervous system.

Advances in noninvasive methods for diagnosing nonalcoholic fatty liver disease.

The prevalence of nonalcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases worldwide, has been increasing. In terms of pathological changes, NAFLD can be divided into simple steatosis, nonalcoholic steatohepatitis (NASH) and liver cirrhosis. Hepatocyte damage and inflammatory activity are the main characteristics for evaluating the progress of liver disease. Early and effective diagnosis of the disease is quite important. Pathological findings based on liver biopsy or resected specimens are considered the gold standard for diagnosing and staging steatosis, fibrosis and cirrhosis; however, it is invasive and may lead to related complications. Non-imaging methods such as clinical features and biochemical tests, and imaging methods such as ultrasonography, FibroScan, computed tomography and magnetic resonance imaging are the commonly used noninvasive alternatives, being relatively novel, safe and reliable. In this review, we summarized the benefits and shortcomings of these non-invasive methods for the evaluation of NAFLD.