Keisuke Kakisaka

Changes in liver function parameters after percutaneous radiofrequency ablation therapy in patients with hepatocellular carcinoma

Aim:  To evaluate changes in liver function parameters and risk factors 1 year after percutaneous radiofrequency ablation (RFA) therapy in patients with hepatocellular carcinoma (HCC).

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.

Visualizing the hepatic vascular architecture using superb microvascular imaging in patients with hepatitis C virus: A novel technique.

AIM To identify the hepatic vascular architecture of patients with hepatitis C virus (HCV) using superb microvascular imaging (SMI) and investigate the use of SMI in the evaluation of liver fibrosis. METHODS SMI was performed in 100 HCV patients. SMI images were classified into five types according to the vascular pattern, and these patterns were compared with the fibrosis stage. Moreover, the images were analyzed to examine vascularity by integrating the number of SMI signals in the region of interest ROI [number of vascular trees (VT)]. The number of VT, fibrosis stage, serum parameters of liver function, and CD34 expression were investigated. RESULTS There was a significant difference between SMI distribution pattern and fibrosis stage (P < 0.001). The mean VT values in each of the fibrosis stages were as follows: 26.69 ± 7.08 in F0, 27.72 ± 9.32 in F1, 36.74 ± 9.23 in F2, 37.36 ± 5.32 in F3, and 58.14 ± 14.08 in F4. The VT showed excellent diagnostic ability for F4 [area under the receiver operator characteristic (AUROC): 0.911]. The VT was significantly correlated with the CD34 labeling index (r = 0.617, P < 0.0001). CONCLUSION SMI permitted the detailed delineation of the vascular architecture in chronic liver disease. SMI appears to be a reliable tool for noninvasively detecting significant fibrosis or cirrhosis in HCV patients.

Predictive formula for acute liver failure is useful for predicting the prognosis of patients with acute-on-chronic liver failure

The prognosis of acute‐on‐chronic liver failure (ACLF) is extremely poor in comparison to acute liver failure (ALF). We aimed to establish methods for the early diagnosis of ACLF and its severity to identify the patients with a poor prognosis.

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).

Identification of amino acids in antigen-binding site of class II HLA proteins independently associated with hepatitis B vaccine response

BACKGROUND & AIMS Genetic factors in class II human leukocyte antigen (HLA) have been reported to be associated with inter-individual variation in hepatitis B virus (HBV) vaccine response. However, the mechanism underlying the associations remains elusive. In particular, the broad linkage disequilibrium in HLA region complicates the localization of the independent effects of genetic variants. Thus, the present study aimed to identify the most probable causal variations in class II HLA loci involved in the immune response to HBV vaccine. METHODS We performed a case-control study to assess whether HLA-DRB1, -DQB1, and -DPB1 4-digit alleles were associated with the response to primary HBV vaccination in 574 healthy Japanese students. To identify causative variants, we next assessed independently associated amino acid variants in these loci using conditional logistic regression analysis. Furthermore, to clarify the functional effects of these variants on HLA proteins, we performed computational structural studies. RESULTS HLA-DRB1∗01:01, HLA-DRB1∗08:03, HLA-DQB1∗05:01, and HLA-DPB1∗04:02 were significantly associated with sufficient response, whereas HLA-DPB1∗05:01 was associated with poor response. We then identified amino acids independently associated with sufficient response, namely, leucine at position 26 of HLA-DRβ1 and glycine-glycine-proline-methionine at positions 84-87 of HLA-DPβ1. These amino acids were located in antigen-binding pocket 4 of HLA-DR and pocket 1 of HLA-DP, respectively, which are important structures for selective binding of antigenic peptides. In addition, the detected variations in HLA-DP protein were responsible for the differences in the electrostatic potentials of the pocket, which can explain in part the sufficient/poor vaccine responses. CONCLUSION HLA-DRβ1 position 26 and HLA-DPβ1 positions 84-87 are independently associated with anti-HBs production against HBV vaccine. Our results suggest that HBsAg presentation through these HLA pocket structures plays an important role in the inter-individual variability of HBV vaccination.

Serum markers for mitochondrial dysfunction and cell death are possible predictive indicators for drug-induced liver injury by direct acting antivirals

We prospectively screened patients treated with direct‐acting antivirals (DAA) in order to detect and analyze serum markers that are present prior to the development of drug‐induced liver injury (DILI).

Elevation of serum cytokines preceding elevation of liver enzymes in a case of drug‐induced liver injury

A 50‐year‐old man who was being treated for both pneumonia and type 2 diabetes mellitus complained of abdominal distention on the 16th hospital day. Liver enzyme elevation without symptoms was detected on the 17th hospital day. Based on a Roussel Uclaf Causality Assessment Method score of 10 and a Japan Digestive Disease Week score of 9, we diagnosed the patient as having drug‐induced liver injury (DILI). Simultaneous assays of the levels of cytokines revealed that the elevation of the levels of interleukin (IL)‐1β, IL‐10, IL‐12, IL‐13 and tumor necrosis factor‐α preceded the elevation of the serum liver enzymes. This case suggests that some cytokines or related molecules are potentially useful as early‐phase biomarkers for DILI.