Shigehiro Kokubu

Close association between high serum ALT and more rapid recurrence of hepatocellular carcinoma in hepatectomized patients with HCV-associated liver cirrhosis and hepatocellular carcinoma.

We investigated whether or not a high serum alanine aminotransferase (ALT) level is associated with a more rapid recurrence of hepatocellular carcinoma (HCC) in hepatectomized patients with hepatitis C virus (HCV)-associated liver cirrhosis (LC) (HCV-LC) and HCC. Thirty-three hepatectomized patients with HCV-LC and HCC of a single nodule who had no histologic evidence of portal or hepatic vein invasion and who had been followed up for more than 3 years were included in the study. They were subdivided into two groups according to their serum ALT levels, ALT being a well-known marker of inflammatory necrosis in the liver. Seventeen patients whose serum ALT levels showed several peaks or plateaus above 80 international units (IU) were designated as the high ALT group, and 16 patients whose serum ALT levels showed a sustained low level below 80 IU until the first recurrence were designated as the low ALT group, and the interval between hepatectomy and the first recurrence was observed. In the high ALT group, HCC recurred within 3 years in 70.6% of the patients. In contrast, it recurred in only 18.8% of the low ALT group within the same period (p < 0.05). There was a significant difference (p = 0.0201) between the two groups in the cumulative nonrecurrence rate. The mean interval in recurrent patients between hepatectomy and the first recurrence in the high ALT group (23.6 ± 2.8 months; mean ± SE) was significantly (p < 0.02) shorter than that in the low ALT group (49.3 ± 9.7 months). The expected interval between hepatectomy and recurrence was as short as 2.8 ± 0.5 years (mean ± SE) in the high ALT group, compared with 5.8 ± 0.7 years in the low ALT group (p < 0.05). These results showed that the recurrence of HCC was accelerated in the high ALT group, suggesting that suppression of the rise in ALT level after hepatectomy by treatment with anti-inflammatory drugs may prolong the interval until recurrence by about 2 years in hepatectomized patients with HCC and HCV-LC.

Restoration of thrombopoietin production after partial splenic embolization leads to resolution of thrombocytopenia in liver cirrhosis

The aim of this study was to evaluate the relation between thrombopoietin (TPO) and thrombocytopenia in patients with liver cirrhosis and those with idiopathic portal hypertension (IPH) before and after partial splenic embolization (PSE). We examined changes in platelet counts, liver function, megakaryocyte function, and plasma TPO levels after PSE in 30 patients (20 with liver cirrhosis, and 10 with IPH). Platelet counts in both cirrhosis and IPH increased significantly 2 months after PSE (cirrhosis group, 4.0+/-1.9 vs. 7.5+/-4.4x10(4)/&mgr;l: P=0.0002; IPH group, 4.0+/-1.7 vs. 6.5+/-2.3x10(4)/&mgr;l: P=0.0042). Plasma TPO level and prothrombin time increased significantly and alanine aminotransferase level (ALT) and total bilirubin level decreased significantly 2 months after PSE in the cirrhosis group (plasma TPO level, 0.57+/-0.30 vs. 0.72+/-0.27 fmol/ml: P=0.024), but not in the IPH group (0.56+/-0.21 vs. 0.55+/-0.34 fmol/ml: P=0.94). Moreover, the score of megakaryocytes with platelet production, an index of platelet production by megakaryocytes in bone marrow, increased significantly in the cirrhosis group. TPO production in cirrhotic patients is restored after PSE, leading to the resolution of thrombocytopenia. But patients with IPH had no change in liver function, indicating that only decreased spleen volume was responsible for the improvement in platelet count.

A Combination Therapy With Simvastatin and Ursodeoxycholic Acid Is More Effective for Cholesterol Gallstone Dissolution Than Is Ursodeoxycholic Acid Monotherapy

Inhibitors of 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase have been reported to decrease the cholesterol saturation index (CSI) in duodenal bile in humans and to prevent formation of cholesterol gallstones in animal studies. We performed a prospective study to evaluate the role of HMG-CoA reductase inhibitors as gallstone-dissolving agents. Fifty patients with radiolucent gallstones in a gallbladder opacifying at drip infusion cholecystography were treated with either 10 mg/day simvastatin plus 600 mg/day ursodeoxycholic acid (group 1, n=26) or 600 mg/day ursodeoxycholic acid alone (group 2, n=24) for 12 months. The ratio of solitary to multiple gallstone cases was 21:29. Plasma lipid levels were assessed and ultrasonographic examination of the gallbladder was performed at baseline and at 3-month intervals during treatment. Duodenal bile sampling was performed in five patients in each group at baseline and after 12 months of treatment. Plasma cholesterol decreased significantly in group 1 but not in group 2. In solitary gallstone cases, no significant difference in dissolution rates was observed between groups 1 (3 of 9, 33%) and 2 (4 of 12, 33%). In contrast, the dissolution rate in multiple gallstone cases was significantly higher in group 1 (12 of 17, 71%) than in group 2 (3 of 12, 25%) (p < 0.01). Bile cholesterol saturation index was significantly decreased (p < 0.01) but did not significantly differ between the two groups. These results suggest that combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than ursodeoxycholic acid monotherapy in patients with multiple gallstones.

Serum alanine aminotransferase levels and survival after hepatectomy in patients with hepatocellular carcinoma and hepatitis C virus-associated liver cirrhosis.

We examined whether sustained alleviation of inflammation as monitored by serum alanine aminotransferase (ALT) levels was associated with longer survival in hepatectomized hepatocellular carcinoma (HCC) patients with hepatitis C virus‐associated liver cirrhosis (HCV‐LC). Thirty‐four hepatectomized patients with HCV‐LC and HCC as a single nodule, and for whom more than 5 years had elapsed after the hepatectomy, were studied. They had no histologic evidence of portal or hepatic vein invasion. They were subdivided into two groups according to their serum ALT levels in the 2 years after hepatectomy: the low ALT group comprised 13 patients whose serum ALT levels showed a sustained low level below 80 IU, and the high ALT group comprised 21 patients whose serum ALT levels showed several peaks or plateaus above 80 IU. The patients had been followed‐up prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography for recurrence for >5 years. The survival period, non‐recurrence interval and number of recurrences were observed. Recurrences were treated with transcatheter chemoembolization in all cases. The cumulative survival rate in the low ALT group was significantly better than that in the high ALT group (P<0.05). The 5‐year survival in the low ALT group was as high as 92.3% (12 of 13) compared with 33.3% (7 of 21) in the high ALT group (P<0.05). The cumulative non‐recurrence rate in the low ALT group was also significantly better than that in the high ALT group (P<0.01). The survival period correlated well with the interval until the first recurrence (r=0.545, P=0.006). There was a tendency for the number of recurrences in the low ALT group (1.5±0.4, mean±SE) to be fewer than that in the high ALT group (2.2±0.4), although this was not significant. Sustained alleviation of inflammation, as indicated by low ALT levels, provides a survival advantage mainly due to the longer non‐recurrence interval, and possibly because of fewer recurrences, in hepatectomized HCC patients with HCV‐LC.

Hematoma with High Oxygen Partial Pressure Resulting from Injection Sclerotherapy for Esophageal Varices — Report of a Case

Abstract: Endoscopic injection sclerotherapy (EIS) was performed on a 44‐year‐old Japanese male, who had been suffering from risky esophageal varices due to cirrhosis of the liver. Blood gas analysis at the beginning of therapy showed that the partial pressure of oxygen at the variceal (PO2) and arterial blood (PaO2) were 47.2 mmHg and 64.1 mmHg, respectively. Sclerosant with contrast medium was injected into the varices and the left gastric vein was embolized; this was always confirmed by endoscopic varicealography during injection scleorotherapy (EVIS). During the fifth EIS session, there was evidence of pooling of contrast medium with sclerosant and an intramural hematoma had developed, which could not be reduced by puncture. The blood gas analysis showed a drastic increase in PO2 (107.9 mmHg), whereas PaO2 remained mostly unchanged (58.8 mmHg). To our knowledge, this is the first report of blood gas analysis during hematoma and the high PO2 compared with PaO2 indicated that there was a substantial inflow of oxygen‐rich blood, possibly from the pulmonary vein into the varices. This inflow of blood into the varices may have contributed to the formation of the large hematoma in small varices following EIS. (Dig Endosc 1999; 11: 55–61)