Chitomi Hasebe

Dose‐finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A randomized, double‐blind, placebo‐controlled trial

Liver cirrhosis represents the end stage of any chronic liver disease, and it is associated with hepatic edema such as ascites. Many patients with ascites do not respond to diuretic therapy or require administration of diuretics at high doses that can cause adverse events. This 7‐day, multicenter, double‐blind trial of tolvaptan was designed to determine the optimal dose of tolvaptan for producing the intended pharmacological effect in hepatic edema.

Augmented hepatic Toll-like receptors by fatty acids trigger the pro-inflammatory state of non-alcoholic fatty liver disease in mice.

There is considerable evidence that intestinal microbiota are involved in the development of metabolic syndromes and, consequently, with the development of non‐alcoholic fatty liver disease (NAFLD). Toll‐like receptors (TLRs) are essential for the recognition of microbiota. However, the induction mechanism of TLR signals through the gut‐liver axis for triggering the development of non‐alcoholic steatohepatitis (NASH) or NAFLD remains unclear. In this study, we investigated the role of palmitic acid (PA) in triggering the development of a pro‐inflammatory state of NAFLD.

Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside/nucleotide analog therapy

Some patients develop hepatocellular carcinoma (HCC) during nucleoside/nucleotide analog (NA) therapy even if alanine aminotransferase (ALT) or hepatitis B virus (HBV) DNA levels are sufficiently reduced. The aim of this study is to identify the risk factors of development of HCC during NA therapy.

Effects of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma: survey findings of the Japanese Red Cross Liver Study Group.

To investigate, in a large number of cases at multiple institutions, the effects and limitations of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma (HCC) in clinical practice.

Characteristics of the PIVKA-II found in hepatocellular carcinoma, investigation using monoclonal antibodies MU-3 and 19B7

Abstract We classified PIVKA-II into two subtypes using a new monoclonal antibody (19B7) to PIVKA-II and a previously available monoclonal antibody (MU-3) and demonstrated differences in composition of PIVKA-II subtypes between HCC and benign liver diseases. These two monoclonal antibodies recognize almost the same site of PIVKA-II molecule, and the three-dimensional conformation of this site due to Gla formation might be important in differences of recognition by the two antibodies.

Long‐term follow up of peginterferon‐α‐2a treatment of hepatitis B e‐antigen (HBeAg) positive and HBeAg negative chronic hepatitis B patients in phase II and III studies

We analyzed the 5‐year post‐treatment response to peginterferon α‐2a (PEG IFN‐α‐2a) in hepatitis B e‐antigen (HBeAg) positive and negative chronic hepatitis B patients.

Efficacy of daclatasvir plus asunaprevir in patients with hepatitis C virus infection undergoing and not undergoing hemodialysis: Daclatasvir plus asunaprevir in non-HD and HD patients

To evaluate the virologic responses and clinical course of daclatasvir plus asunaprevir treatment in non‐hemodialysis (non‐HD) and hemodialysis (HD) patients infected with genotype 1 hepatitis C virus (HCV).

Importance of cytotoxic T lymphocytes in the rejection of transplanted hepatocellular carcinoma.

Fischer rats became resistant to syngeneic hepatocellular carcinoma (FAA-HTC1) cells on repeated sensitization with mitomycin C-treated FAA-HTC1 cells. In contrast, FAA-HTC1 cells injected into the liver killed normal control Fischer rats within 2 months. Histopathological studies revealed massive accumulation of mononuclear cells in the tumor tissues of sensitized rats that rejected syngeneic FAA-HTC1 cells, whereas very few mononuclear cells were found in the tumor tissues of control rats. Cell populations infiltrating the tumor tissues were identified by flow cytometric analysis. Mononuclear cells found within the regressing tumors of the sensitized rats were identified as mostly T cells, and two-thirds of these T cells were CD8-positive. Compared with the activity in control rats, the killer activity of mononuclear cells infiltrating tumors was significantly increased in the sensititized rats 7 days after tumor inoculation. Depletion of CD8(+) T cells significantly reduced the cytotoxicity of mononuclear cells infiltrating tumors obtained from sensitized rats. In contrast, depletion of CD16(+) cells reduced the cytotoxicity of mononuclear cells infiltrating tumors obtained from both control and sensitized rats. Furthermore, the CD16(+) cell-depleted fraction of mononuclear cells infiltrating tumors showed significant cytotoxicity against FAA-HTC1 cells, but failed to show cytotoxicity against other syngeneic tumor cells or allogeneic hepatoma cells.

Polymorphism of Receptor-Type Tyrosine-Protein Phosphatase Delta gene in the development of non-alcoholic fatty liver disease

Some single‐nucleotide polymorphisms (SNPs) are associated with the development of non‐alcoholic fatty liver disease (NAFLD). As one of the genetic factors, PNPLA3 rs738409 (I148M) is important to associate with pathogenesis of NAFLD. Because other SNPs remain unclear in Japan, we performed a high‐throughput sequencing that targeted more than 1000 genes to identify a novel genetic variant in Japanese patients with NAFLD.

Effectiveness of pazopanib for postoperative recurrence of granulocyte colony-stimulating factor-producing primary hepatic angiosarcoma

A 38-year-old Japanese woman was referred to our hospital with complaints of fever, general fatigue, and upper abdominal discomfort. Computed tomography revealed a massive tumor in the right lobe of the liver, and laboratory data demonstrated increased white blood cell (WBC) count and serum granulocyte colony-stimulating factor (G-CSF) level. An extended right hepatectomy was performed, and pathological examination revealed spindle-shape tumor cells that formed vessel-like structures that were compatible with hepatic angiosarcoma. As a rapid recurrence occurred after surgery, S-1 was administered as a first-line chemotherapy, and weekly paclitaxel was administered as the second-line chemotherapy. However, patient eventually became resistant to these therapies. Therefore, pazopanib, a multitargeted tyrosine kinase inhibitor, was administered, after which both the WBC count and G-CSF level rapidly decreased. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed decreased FDG uptake. This is the first report on the administration of pazopanib as a third-line chemotherapeutic agent for treating G-CSF-producing primary hepatic angiosarcoma. The efficacy of this therapy was demonstrated with FDG-PET.