Toshifumi Kashiwabara

Plasma abnormal prothrombin (PIVKA‐π): A new and reliable marker for the detection of hepatocellular carcinoma

We evaluated the clinical usefulness of a protein induced by vitamin K absence, antagonist‐prothrombin (PIVKA‐π), in detecting hepatocellular carcinoma (HCC) specifically in patients with liver cirrhosis, and the possible correlation between levels of PIVKA‐π and pathological features of HCC. Plasma levels of PIVKA‐π and α‐fetoprotein (AFP) were measured in 628 patients with various diseases, including 253 with liver cirrhosis and 116 with HCC. PIVKA‐π was detected (≥ 0.1 arbitrary unit/mL) in 54.3% of HCC and the concentration showed a positive correlation with the tumour size. As a screening test for the detection of HCC, PIVKA‐π produced values comparable with those of AFP with a sensitivity, specificity and validity of 52.8, 98.8 and 51.6% respectively. Sixteen of 45 patients (37%) with HCC who had low AFP (< 100 ng/mL) levels were positive for PIVKA‐π. No apparent relationship, however, could be found between the levels of PIVKA‐π and the aetiology or pathological findings of HCC. These results suggest that PIVKA‐π can be a reliable marker for detecting HCC in patients with liver cirrhosis.

Usefulness of antithrombin III and α2-plasmin inhibitor in early differentiation of fulminant hepatitis and severe form of acute hepatitis

SummaryTo evaluate the usefulness of antithrombin III (AT III) and α2 -plasmin inhibitor (α2PI) in early differential diagnosis of fulminant hepatitis from the severe form of acute hepatitis, the activities of AT III and α2PI were measured in plasma of 15 patients with fulminant hepatitis and 6 patients with severe form of acute hepatitis. The activities of prothrombin time (PT), hepaplastintest (HPT) and thrombotest (TT) were also evaluated. The mean values and the standard errors (SE) for PT, HPT and TT were 21.1 ±2.6%, 14.0 ±1.6% and 10.3 ±1.7%, respectively, in the early stage of fulminant hepatitis and 25.3 ±2.4%, 21.6 ±4.6% and 15.8 ±3.6%, respectively, in the severe form of acute hepatitis. No significant difference in the tests between these two diseases was noted. On the other hand, the mean values ±SE for AT III and α2PI were 13.7 ±4.6% and 25.6 ±8.6% in fulminant hepatitis and 70.2 ±28.5% and 98.7 ±9.7% in the severe form of acute hepatitis. A significant difference between the two diseases was observed. From the above, it is concluded that measuring AT III and α2Pl along with PT, HPT and TT is useful for early diagnosis of fulminant hepatitis.

Clinical evaluation of tissue plasminogen activator (t-PA) levels in patients with liver diseases

SummaryTissue plasminogen activator (t-PA) levels in plasma or serum were studied in 416 patients with liver diseases: acute hepatitis (AH, n=30); fulminant hepatitis (FH, n=36); chronic inactive hepatitis (CIH, n=57); chronic active hepatitis (CAH, n=39); compensated liver cirrhosis (cLC, n=78); decompensated liver cirrhosis (dLC, n=84); hepatocellular carcinoma (HCC, n=64); advanced hepatocellular carcinoma (aHCC, n=28); and compared with that of a control group (n=106) of healthy subjects. The t-PA levels showed significant increase in patients with AH, FH, CAH, cLC, dLC and HCC, compared with normal controls. The abnormal rates in t-PA levels (higher than 8.3 ng/ml) for each type of liver diseases were 86.1% in FH, 46.2% in CAH, 50% in cLC, 85.7% in dLC, 67.2% in HCC, and 89.3% in aHCC. t-PA levels tended to be higher in more advanced liver diseases. t-PA levels significantly correlated positively with plasminogen activator inhibitor (PAI-1) in AH, cLC, dLC, HCC and aHCC, and negatively with plasmin arplasmin inhibitor complex (PIC), plasminogen (Pig), FDP, AT III and α2-plasmin inhibitor (α2-PI) in dLC, prothrombin time (PT) and fibrinogen (Fbg) in HCC. t-PA levels in patients with FH, CAH and dLC were significantly higher than those in patients with AH, CIH and cLC, respectively. Moreover, the changes of t-PA levels in the clinical courses of various liver diseases revealed that t-PA levels increased sensitively with progression of liver diseases or in advanced liver diseases. These results suggest that t-PA has a potential clinical use to judge the prognosis of liver diseases and is a sensitive marker for severe liver diseases from tjie standpoint of coagulofibrinolysis, especially in relation to PAI-I.

Two cases of severe hepatitis B by familial transmission.

HBe抗体陽性キャリア妊婦から垂直感染し出生50日目に出生児が急性B型肝炎を発症し,さらに患児の発症から92日目に父親がB型劇症肝炎を発症し救命しえた家族内感染例を経験した.患児は発熱・哺乳力の低下で発症.GOT 11,380U, GPT 5,060Uと上昇しプロトンビン時間(PT)10%と著明な低下を示した.HBs-Ag陽性,anti HBc (200倍)74%であった.総ビリルビン(T. Bil)が漸増し32mg/dlとなり凝固能の改善がないため,プレドニゾロンを使用したところ改善し,急性肝炎重症型と考えられた.父親は嘔気・全身倦怠感で発症.T. Bil 14.7mg/dl, GOT 1,675U, GPT 4,690U, PT12%, HBsAg陽性,IgMHBc3.29と陽性.昏睡II度となりプレドニゾロン,グルカゴン-インスリン療法,特殊組成アミノ酸などの治療にて改善した.母親から出生児に垂直感染し,患児から父親に水平感染したと思われる.HBe抗体陽性キャリア妊婦からの出生児に対してもHBIGなどの対策が必要と考えられる症例である.