Mio Onodera

Alpha‐fetoprotein: A biomarker for the recruitment of progenitor cells in the liver in patients with acute liver injury or failure

The optimal conditions for hepatocyte proliferation should be clarified in an attempt to improve the impaired liver regeneration observed in patients with acute liver failure (ALF). In order to evaluate the significance of the serum α‐fetoprotein (AFP). level and prothrombin time international normalized ratio (PT‐INR) as possible biomarkers of the proliferation of liver stem/progenitor cells (LPC) and mature hepatocytes (MH), respectively, we focused on donors of living donor liver transplantation (LDLT) and patients with acute liver injury (ALI), including ALF.

Serial changes of liver stiffness measured by acoustic radiation force impulse imaging in acute liver failure: A case report

Acoustic radiation force impulse (ARFI) imaging is a new technology used to determine liver elasticity. We report the case of a patient that survived hyperacute‐type acute liver failure (ALF) and who showed a dramatic change in the value of shear wave velocity (SWV) measured by ARFI, which corresponded with the severity of her liver damage. The value of SWV increased significantly up to 3.6 ± 0.3 m/s during the encephalopathy phase and then decreased along with the recovery of liver function, the blood flow of the right portal vein, and the liver volume. These findings suggest the value of SWV in ALF as a reliable marker of liver tissue damage. Further investigations of the pathophysiological significance of SWV in ALF are warranted.

Liver stiffness measured by acoustic radiation force impulse elastography reflects the severity of liver damage and prognosis in patients with acute liver failure

We measured liver stiffness (LS) in patients with acute liver failure (ALF) using acoustic radiation force impulse (ARFI) elastography and investigated the usefulness of measuring LS for predicting the prognosis of ALF patients.

Differential evaluation of hepatocyte apoptosis and necrosis in acute liver injury

Aim:  The significance of cytokelatin‐18 fragment cleaved by caspase‐3 (CK‐18‐fr) and high mobility group box‐1 (HMGB‐1) were evaluated experimentally and clinically for the differential evaluation of hepatocyte apoptosis and necrosis in patients with acute hepatic injury (AHI).

Icteric acute hepatitis E with no response of immunoglobulin M class anti‐hepatitis E virus antibody

A 68‐year‐old Japanese man developed icteric acute hepatitis during periodic care after undergoing gastrectomy due to early gastric cancer. The routine serological markers for hepatitis A, B and C viruses were all negative. Although the liver enzymes spontaneously recovered without any specific therapy, cholestasis was relatively prolonged and successfully treated with prednisolone. Determination of serum hepatitis E virus (HEV) RNA revealed the transient infection of HEV, and both immunoglobulin (Ig)A and IgG class anti‐HEV antibodies were detected after the disease onset, whereas those were negative when measured 3 weeks prior to the onset. In addition, the titer of serum IgA class antibody was associated with the clinical signs of hepatitis. In contrast, no IgM class antibody was detected throughout the course. This case suggests that screening only with IgM class antibody is not sufficient to detect acute HEV infection.

L-carnitine prevents ammonia-induced cytotoxicity and disturbances in intracellular amino acid levels in human astrocytes: L-carnitine protects neurotoxic damage

L‐carnitine (L‐CA) has been used therapeutically to treat hepatic encephalopathy with hyperammonemia, but the mechanism by which L‐CA contributes to ammonia detoxification in the brain is still unclear. Thus, the cytotoxicity and changes in intracellular amino acids (AAs) in astrocytes with hyperammonemia following L‐CA administration were studied.

Predictive biomarkers for diagnosis of minimal hepatic encephalopathy in patients with liver cirrhosis: A preliminary result in a single center study in Japan

Aim: Minimal hepatic encephalopathy (MHE) in liver cirrhosis (LC) is a subclinical abnormality which is only detectable by neuropsychiatric and neurophysiological tests. Reliable predictive biomarkers for diagnosing MHE have not been confirmed. This study examined potential biomarkers to detect MHE in LC patients. Methods: We divided 35 outpatients with LC into two groups based on the presence of MHE according to the results of computer-aided neuropsychiatric testing using four psychometric tests. Differences in clinical and laboratory data were compared between the two groups, and predictive biomarkers for diagnosing MHE were determined using the logistic regression model. Results: The prevalence of MHE in LC was 28.6% (10/35). Clinical features involving Child-Pugh classification and the modified end-stage liver disease score showed no differences between the MHE-positive and MHE-negative patients. Among biochemical parameters, elevated plasma ammonia level (P=0.034), increased creatinine (P=0.008), and low estimated glomerular filtration rate (P=0.042) showed greater significance in MHE-positive patients compared with MHE-negative patients. However, univariate and multivariate analysis showed that ammonia level (odds ratio, 1.023 and 1.031, respectively; 95% confidence interval of coefficient estimate, 1.005-1.041 and 1.006-1.058, respectively) was the only significant independent predictor for the detection of MHE. Conclusion: Plasma ammonia level may be useful as a predictive biomarker to prediagnose the neuropsychiatric test-based diagnosis of MHE. Our results also reinforce previous findings on crucial roles for renal ammonia metabolism and urinary excretion in patients with LC. Correspondence to: Kazuyuki Suzuki, M.D., Ph.D., Department of Nutritional Science, Morioka University, Sunakomi 808, Takizawa, Iwate 020-0694, Japan, Tel: 081-19-688-5555, Fax: 081-19-688-5577; E-mail: kasuzuki@morioka-u.ac.jp