Hepatocarcinogenesis in non-alcoholic fatty liver disease in Japan.

In Japan, there has been a gradual increase in cases of non-viral chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), occurring with hepatocellular carcinoma (HCC). First, a national survey investigating the etiology of HCC in Japan was performed. Among HCCs based on non-viral disease, alcoholic liver disease with HCC accounted for 7.2% of all HCCs, followed by chronic liver disease of unknown etiology with HCC (5.1%) and NAFLD with HCC (2.0%). The clinical characteristics of these three HCC groups were clearly different. In our second analysis, the HCC development rates among liver cirrhosis with NAFLD, alcoholic cirrhosis, and cirrhosis with hepatitis C virus (HCV) were compared. HCC development rates were 11.3%/5 years in NAFLD cirrhosis, 30.5%/5 years in HCV cirrhosis, and 12.5%/5 years in alcoholic cirrhosis, suggesting that the hepatocarcinogenesis in NAFLD and alcoholic liver disease were similar but were lower than that in HCV. Using Cox hazards analysis, older age, higher serum γ-glutamyl transpeptidase level, and higher Child-Pugh score as risk factors of HCC were identified. Finally, clinical data of NAFLD-HCC with the data for HCC with HCV (HCV-HCC) were compared. The percentage of NAFLD-HCC patients with des-gamma-carboxy prothrombin-positive was higher than that with α-fetoprotein-positive. The 5-year survival and recurrence rates for NAFLD-HCC were almost similar to those for HCV-HCC. In Asian countries, the prevalence of NAFLD is increasing. Therefore, elucidating the pathogenesis and clinical features of HCC in patients with NAFLD is indeed an urgent problem.

Late delirious behavior with 2009 H1N1 influenza: mild autoimmune-mediated encephalitis?

Delirious behavior associated with influenza usually has an onset within a few days after fever and lasts <24 hours. As we encountered several patients with 2009 H1N1 influenza who presented with late-onset and long-standing delirious behavior, we retrospectively evaluated the clinical, radiologic, and laboratory features to elucidate the possible pathophysiology. This information was collected on 5 previously healthy patients (2 boys and 3 girls, aged 10-15 years) with 2009 H1N1 influenza who presented with late onset (>3 days after fever) and long-standing (>48 hours) delirious behavior. Each exhibited mild to moderate drowsiness between the episodes of delirious behavior. Electroencephalography was normal except for 1 patient with high voltage and slow activity bilaterally in the occipital regions. Brain MRI was normal. The outcome was excellent with no neurologic sequel in 4 of the 5 patients. In all 5 patients, autoantibodies against N-methyl-D-aspartate type glutamate receptor were elevated or positive in cerebrospinal fluid or serum; the autoantibody levels normalized in the 3 patients who had follow-up studies. This study indicates that 2009 H1N1 influenza has a tendency to cause late-onset and long-standing delirious behavior, at least in Japanese children. Mild autoimmune-mediated encephalitis should be considered as an underlying cause.

Serum and cerebrospinal fluid S100B, neuron-specific enolase, and total tau protein in acute encephalopathy with biphasic seizures and late reduced diffusion: a diagnostic validity.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized clinically by biphasic seizures and late magnetic resonance imaging abnormalities, such as reduced subcortical diffusion from day 3 onwards, often accompanied with some neurological sequelae. In the early stages of the disease, AESD closely resembles its far more prevalent and relatively benign counterpart, febrile seizure (FS). METHODS: We measured and compared the serum or cerebrospinal fluid (CSF) levels of S100B, neuron-specific enolase (NSE), and total tau protein in 43 patients with FS and 18 patients with AESD, at any point during the disease. To assess early diagnostic validity, we compared these biomarkers in 43 FS and eight AESD patients, with whom the day 0-2 samples were available. We used the receiver-operator characteristic curve to evaluate the diagnostic values of these markers. RESULTS: The levels of all biomarkers were significantly higher in AESD than FS patients. When only day 0-2 samples from AESD patients were used, the levels of all the measured biomarkers, except serum NSE, were still significantly higher in patients with AESD than in FS, suggesting that AESD could damage astrocytes, neurons, and axons, even in the early stages of the disease. According to the receiver-operator characteristic curve analyses, CSF S100B (cut-off value, 100 pg/mL) and CSF total tau protein (cut-off value, 100 pg/mL) were better predictors of AESD than other biomarkers. CONCLUSION: The combination of CSF S100B and CSF total tau protein resulted in a positive predictive value of AESD 83.3%, which could be helpful for early diagnosis, facilitating early therapeutic interventions.