Kenji Umeda

Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C

Background and aims: MicroRNAs are small non‐coding RNA molecules that post‐transcriptionally regulate gene expression. Liver‐specific microRNA‐122 (miR‐122) has been shown to facilitate the replication of hepatitis C virus (HCV) in human hepatoma cells in vitro. However, the clinical significance of hepatic miR‐122 on HCV in human body is unclear.

Fascin expression in progression and prognosis of hepatocellular carcinoma

Fascin is an actin‐bundling protein and induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been reported to be associated with progression or prognosis in various neoplasms, but the role of fascin in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate the clinicopathological and prognostic relevance of fascin by immunohistochemistry.

Congestion of the donor remnant right liver after extended left lobe donation.

The clinical importance of congestion of the remnant right lobe has not yet been fully elucidated in donors who donate their left lobe with the middle hepatic vein. The impact of congestion on clinical course and liver regeneration in 52 donor remnant livers were evaluated. The donors were divided into three groups according to the degree of the congestion: the mild [congestion ratio (CR) < 10%], moderate (CR ranged from 10% to 25%) and severe congestion groups (CR > 25%). The regeneration ratio of the graft at postoperative day 7 (7 POD) was 22.0 ± 14.3% and inversely correlated with the CR in the remnant right lobe (P = 0.003). Aspartate aminotransferase and alanine aminotransferase at 7 POD were significantly higher in the severe CR group in comparison to the mild CR group (P = 0.003 and 0.019, respectively), but those of the three groups were comparable at 30 POD. The hospital stays were significantly longer in the severe CR group (P = 0.010). In conclusion, the congestion of the donors’ remnant right liver can lead the transient liver dysfunction and poor regeneration. Therefore, the conversion of the graft from the left to right lobe might be appropriate according to the degree of the congestion.

Impact of preoperative serum sodium concentration in living donor liver transplantation.

Background and Aims:  The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre‐transplant sodium concentration on postoperative clinical outcomes.

Successful curative extracorporeal hepatic resection for far‐advanced hepatocellular carcinoma in an adolescent patient

Hepatectomy is the principal treatment for hepatocellular carcinoma (HCC); however, some HCCs are not resectable by conventional hepatic resection. In such apparently incurable cases, extracorporeal hepatic resection (ECHR) may offer an option for survival. We recently encountered a juvenile patient with faradvanced HCC who was successfully treated by ECHR with favorable long-term survival. A 17-year-old woman was referred to our hospital with a huge liver mass and was admitted for evaluation. She had no history of serious illness, surgery, or hospitalization and no notable family history. Of the serum tumor markers examined, a-fetoprotein (335.5 ng/mL, normal < 20 ng/mL) and des-c-carboxy prothrombin (1988 mAU/mL, normal < 40 mAU/mL) were elevated. She was serologically negative for anti– hepatitis C virus antibody and hepatitis B surface antigen, but she was positive for hepatitis B core antigen. Computed tomography with contrast enhancement showed an 18 cm 12 cm tumor in the center of the liver (Fig. 1a). One intrahepatic metastatic tumor was found in the left lateral segment of the liver. The first left branch of the portal vein was completely involved in the liver. The inferior vena cava (IVC) and the right hepatic vein (RHV) were completely surrounded by the tumor and were remarkably dislocated to the anterior side of the body (Fig. 1b,c). Celiac arterial angiography and indirect portography revealed an intact hepatic artery and the portal vein of the right posterior branch (Fig. 1d,e). The estimated remnant liver volume after left trisegmentectomy was 508 mL, which corresponded to 52.6% of the patient’s standard liver volume (Fig. 1f). On the basis of these findings, standard in situ hepatic resection was considered unfeasible, and ECHR was planned instead. Laparotomy revealed that the liver was severely enlarged because of the huge tumor, but the nontumorous liver parenchyma seemed to be normal. After the division of the proper hepatic artery and the common bile duct, the total liver was detached from the diaphragm. Intraoperative ultrasound was used to determine the cutting line at the back table. Vascular clamps were then applied, and this was followed by division of the portal vein and the suprahepatic and infrahepatic IVC, after which total hepatectomy was performed (Fig. 2a). A pump-driven portosystemic venovenous bypass was established from the portal vein and the left saphenous vein to the left axillary vein. The explanted liver was flushed with University of Wisconsin solution. The hepatic parenchymal dissection was performed with a Cavitron ultrasonic surgical aspirator (Valleylab, Inc., Boulder, CO), and the vessels were divided with ligations or clips. The IVC was completely dissected from the tumor and the dorsal liver. Extended left lobectomy with the caudate lobe was performed at the back table. After hepatic resection, vascular and biliary leakage tests were performed by the injection of University of Wisconsin solution, and the leakage points were repaired with fine sutures. The actual weight of the explanted liver was 2050 g (Fig. 2d), and the weight of the liver autograft

Innate memory phenotype CD4+ T cells play a role in early protection against infection by Listeria monocytogenes in a CD30L-dependent manner.

CD30 ligand (CD30L, CD153) is a type II membrane‐associated glycoprotein belonging to the tumor necrosis factor family. It is shown here that CD30L knock out (KO) mice are highly susceptible to primary infection with Listeria monocytogenes as assessed by the survival rate. There were significantly more bacteria on day 3 after infection in the peritoneal cavity, spleen and liver of CD30LKO mice than in wild type (WT) mice. The innate function of memory phenotype (MP) CD44+ CD4+ T cells for interferon‐gamma production was significantly lower in CD30LKO mice than in WT mice in response to interleukin (IL)‐12 and IL‐15 in vitro. Depletion of CD4+ T cells by in vivo administration of anti‐CD4 mAb at an early stage after infection hampered protection against Listeria. Furthermore, in vivo administration of agonistic anti‐CD30 mAb restored protection against Listeria in CD30LKO mice, whereas treatment with soluble mCD30‐Ig hampered protection in WT mice. Taken together, it appears that CD30L/CD30 signaling plays an important role in innate MPCD4+ T cell‐mediated protection against infection with L. monocytogenes.

Early diagnosis and treatment resolved cholestatic hepatitis C without fibrosis after living donor liver transplantation: Report of a case

Cholestatic hepatitis is a life-threatening recurrent pattern of hepatitis C virus (HCV) in immunosuppressed patients, for which curative treatment has not yet been established. We report the successful treatment of cholestatic hepatitis in a 59-year-old man who had undergone right lobe living donor liver transplantation (LDLT) for liver cirrhosis (LC) caused by HCV. Following uneventful surgery and an uncomplicated posttransplant clinical course, there was an abrupt increase in total bilirubin in comparison to aminotransferase on postoperative day (POD) 60 (total bilirubin 16.2 mg/dl, alanine aminotransferase 100 U/l, HCV-RNA 390 kIU/ml). The histological findings of the liver tissue showed lymphocyte infiltration in the periportal zone and severe cholestasis. Considering the clinical course, cholestatic hepatitis was strongly suspected and pegylated interferon and ribavirin therapy was started immediately, resulting in not only a viral response, but minimal progression of fibrosis. This case serves to demonstrate that early diagnosis and timely initiation of optimal antiviral therapy is essential for the resolution of cholestatic hepatitis C.