Shiro Yogita

Mutations of the core gene sequence of hepatitis C virus isolated from liver tissues with hepatocellular carcinoma

Abstract Our preliminary study indicated the presence of a clustering variable region (CVR) in the hepatitis C virus (HCV) core gene sequence in patients with hepatocellular carcinoma (HCC). To compare the sequence divergences of the core gene isolated from cancerous and noncancerous liver tissues in patients with HCC along with those from serum samples in patients with chronic hepatitis (CH), liver cirrhosis (LC), and HCC, we determined nucleotide and deduced amino acid (AA) sequences in a part of the core gene that included the CVR. The sequence diversity in the core gene increased with the progression from CH to LC or HCC and the number of nucleotide substitutions giving rise to changes in AA residues in the CVR was significantly greater in liver tissues than in sera from HCC patients. Moreover, the number of AA residues in the CVR that differed from the representative clone from cancerous liver portions was significantly higher than the number differing from noncancerous portions in each patient. An AA alteration from Gly to Ser at core codon 45 in the CVR was dominant in noncancerous portions rather than in cancerous portions and sera from HCC patients. These findings suggest that a large number of mutations, including biologically important AA sequence changes in the HCV core gene from liver tissue, might be related to hepatocarcinogenesis.

Functional assessment of liver for extended hepatic resection in patients with obstructive jaundice

We studied whether the maximal excretion rate of indocyanine green (ICG Bmax) and the 2-h ICG excretion rate in the bile could be used to estimate the separate functions of the left and right liver in 20 patients with biliary obstruction at the hepatic hilus. ICG Bmax was measured after biliary decompression. An operative procedure that preserved the side of the liver with a positive ICG Bmax value was selected. Eighteen patients tolerated extensive hepatic resection, such as right trisegmentectomy, extended right lobectomy, extended left lobectomy, or left lobectomy. However, prolonged jaundice was observed postoperatively in five of the six patients with 2-h excretion rates of less than 25% and who had undergone extended right lobectomy. One patient on whom extended right lobectomy had been performed died because of postoperative hepatic failure. His ICG Bmax value was +0.6 and his 2-h excretion rate was very low (3%). ICG Bmax and the 2-h excretion rate in the bile reflected well the degree of separate hepatic dysfunction in patients with biliary obstruction at the hepatic confluence. If ICG Bmax value is more than +1.0, resection of more than two segments, such as trisegmentectomy or extended hepatic lobectomy, may be tolerated, and if the ICG Bmax value is positive, hepatic lobectomy may be tolerated. ICG Bmax and 2-h excretion rate in bile are useful indicators of hepatic functional reserve of the separate lobes of the liver in patients with biliary obstruction at the hepatic hilus.

Effects of tacrolimus (FK506) on induction of glutathione S-transferase P-positive foci and liver cell regeneration after partial hepatectomy in F344 rats

The effects of FK506, a potent immunosuppressive drug, on hepatocarcinogenesis were investigated using a medium-term liver bioassay model based on the induction of glutathione S-transferase placental form (GST-P)-positive preneoplastic foci and by studies on liver cell regeneration after two-thirds partial hepatectomy (PH). In Experiment 1, daily FK506 administration, 0.5 or 1.0 mg kg−1 by gastric intubation, increased the areas of GST-P-positive foci in male F344 rats (P<0.05). In Experiment 2, FK506 treatment increased the hepatic 5-bromo-2-deoxyuridine labeling indices on day 1 (P<0.05) and day 2 after PH and the liver weight on day 7 (P<0.01). These results suggest that FK506 has a weak enhancing effect on hepatocarcinogenesis and accelerates liver cell proliferation after hepatectomy.

Successful resection of cholangiocellular carcinoma with tumor thrombus in the main trunk of the portal vein

A space-occupying lesion in the right hepatic lobe, with dilated peripheral bile ducts, was observed by ultrasonography and computed tomography in a 50-year-old man with right upper quadrant abdominal pain. One month later, this lesion evidenced rapid growth and a tumor thrombus, which completely occluded the main trunk and the left primary branch of the portal vein, had developed. The tumor was diagnosed as a cholangiocellular carcinoma with an unusual pattern of intravascular extension. The primary tumor and the portal tumor thrombus were resected via a right hepatic trisegmentectomy combined with resection of the portal vein and extrahepatic bile duct, using a superior mesenteric vein—left femoral vein catheter bypass (SMV—FV bypass). The SMV—FV bypass was found to effectively reduce intraoperative hemorrhage.

Measurement of regional hepatic blood flow by hydrogen clearance method - A comparison of the electromagnetic flowmeter and H2 gas clearance method.

雑種成犬に, 肝動脈・門脈分離測定可能な実験モデルを作成し, 水素ガスクリアランス法 (以下H2法と略す) を用いて, 肝組織血流量を測定し, 電磁流量計による測定値と比較することにより, 次の結論を得た.(1) H2法において, 血流量の算出にはクリアランスカーブが下降し始めて30秒後から2分以内において行うことが適当である.(2) 肝動脈・門脈血流量比は電磁流量計では1対3.3であるのに対し, H2法では1対0.9であり, 門脈血流量はあまり反映されなかった.この原因の1つとして, 門脈血中残存水素濃度の影響が示唆された.