Nobuhisa Kameoka

Effect of Preoperative Portal Vein Embolization on Liver Volume and Hepatic Energy Status of the Nonembolized Liver Lobe in Humans

Clinically portal vein embolization (PVE) is presently preferred to extended hepatectomy. Nevertheless, its effect on hepatic adenosine triphosphate (ATP) and energy charge levels, which are essential for organ viability, has been little studied in humans. Fourteen patients with (n = 7) and without (n = 7) preoperative right PVE participated in this study. Changes in hepatic lobar volume and serum liver function tests were examined before and after percutaneous transhepatic right PVE. Liver volume (cm3) was calculated on computed tomograms before and 20 ± 3 days after PVE. At the time of surgery (mean of 25 days after PVE), small liver specimens were obtained from portal vein (PV) nonembolized left lobes immediately after laparotomy without any ischemic procedures. Concentrations of adenine nucleotides were measured by high performance liquid chromatography, and hepatic energy charge levels were calculated. These values were compared with those in control patients who had not undergone preoperative PVE. Serum liver function tests including the indocyanine green retention rate did not differ significantly before and after PVE. The volume of the PV-nonembolized left lobe significantly increased after right PVE (from 473 ± 32 to 624 ± 66 cm3), with a significant increase in the percentage of the left lobe to total liver volume. The concentrations of AMP, ADP, and ATP, and hepatic energy charge levels in the PV-nonembolized left lobe were similar to those of the control liver. These results suggest that preoperative right PVE increases the volume of the nonembolized left lobe, keeping the hepatic engery charge and ATP levels similar to the control liver, thereby increasing the total amount of ATP and hepatic energy reserve of the PV-nonembolized lobe in proportion to its volume increase at the time of surgery.

Hepatic Adenine Nucleotides and DNA Synthesis during the Regenerative and Atrophic Process of the Liver Lobes after Selective Portal Vein Ligation

Selective portal vein occlusion prior to aggressive hepatic resection is now an alternative way to decrease postoperative morbidity and mortality rates. However, the detailed changes in the hepatic energy status and DNA synthesis rate in both portal vein ligated (PVL) and nonligated (PVNL) lobes of the liver are not clear. In rats, the portal branch that supplies 70% of the liver volume was ligated, and changes in arterial ketone body ratio (AKBR), liver weight, histology, DNA synthesis rate and adenine nucleotides of the PVL and PVNL liver lobes were determined before and 1, 2, 4 and 7 days after portal vein ligation, and compared with those in sham-operated rats. The weight of the PVL lobes decreased, while that of the PVNL lobes increased depending on time. The DNA synthesis rates of the PVNL lobes were significantly higher than those in sham-operated control liver during the first 4 days with the maximal value on the 2nd day, while those of PVL lobes were essentially similar to the control values. Energy charge (EC) in both PVL and PVNL lobes significantly decreased on day 1 and recovered gradually, but with less extent in the regenerating PVNL lobes. The concentrations of total adenine nucleotides (TAN) in both the PVL and PVNL lobes were essentially similar during the first 2 days, but became significantly lower in PVL lobes after day 4. A decrease in EC preceded an increase in DNA synthesis only in the PVNL lobes, in contrast to the PVL lobes. Mitosis of hepatocytes on day 2 and subsequently enlarged lobules with an increased number of hepatocytes were histologic features in the PVNL liver. The AKBR was not correlated with hepatic energy charge of the liver. In conclusion, PVNL liver regenerates preceded by a decrease in EC and a subsequent increase in DNA synthesis keeping TAN constant, while PVL liver becomes atrophic, with a similar change in EC of the PVNL liver but ultimately decreased TAN without any change in DNA synthesis. AKBR is not a parameter reflecting the hepatic EC after portal branch ligation.

Impaired hepatic ketogenesis and regeneration after partial hepatectomy in cirrhotic rats

To examine the difference in hepatic ketogenesis during the regeneration process between cirrhotic and normal liver, arterial ketone bodies (acetoacetate and 3-hydroxybutyrate), free fatty acids and glucose concentrations and liver regeneration rate were determined at 0, 1, 2, 3 and 7 days after partial (70%) hepatectomy in thioacetamide-treated cirrhotic and normal rats. Hepatic ketone body production per unit liver was calculated by total ketone body concentration x blood volume/the remaining liver weight. The regeneration of cirrhotic liver was delayed compared with that of normal liver. In normal rats, total ketone body concentration increased on the 1st day both after hepatectomy and sham operation, and returned to the basal level thereafter. In cirrhotic rats after hepatectomy or sham operation, however, total ketone body concentration did not increase throughout the experimental period although free fatty acids level increased more greatly than in normal rats. Arterial ketone body ratio (acetoacetate/3-hydroxybutyrate) and glucose level decreased on the 1st day after hepatectomy, and recovered after the 2nd day in both cirrhotic and normal rats. Hepatic ketone body production after hepatectomy was significantly greater in normal rats than cirrhotic rats, and hepatectomy itself increased hepatic ketone body production in both rats on the 1st and 2nd postoperative days. In conclusion, hepatic ketone body production is impaired after hepatectomy in cirrhotic rats, which is possibly related to the delayed regeneration of cirrhotic liver.