Kiyoshi Yamazaki

Primary hepatic lymphoma associated with primary biliary cirrhosis

We report a case of primary hepatic lymphoma in a 55-yr-old female patient with primary biliary cirrhosis and Sjögrens syndrome. On July 1994, a tumor measuring 11 mm in diameter was detected in the right lobe of the liver by abdominal ultrasonography. A needle biopsy specimen showed the lesion to contain small- and medium-sized lymphoid cells without obvious atypia, and a provisional diagnosis of pseudolymphoma was made. About 2 yr later, the tumor increased to 15 mm in diameter, necessitating a second needle biopsy. Histological and genetic examinations confirmed non-Hodgkins lymphoma of diffuse, mixed small and large cell, B-cell type. However, the size of the tumor remained almost stable (16 mm in diameter) over a period of 7 months after diagnosis, without any treatment for lymphoma, indicating a low grade malignancy. We document hepatic lymphoma as an additional complication of primary biliary cirrhosis.

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.

Primary biliary cirrhosis an epithelitis: evidence of abnormal salivary gland immunohistochemistry.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology. Nearly 93% of patients with PBC exhibit evidence of focal sialoadenitis. In an earlier study, we reported evidence of aberrant expression of PDC-E2, or a mimeotope, in the salivary glands of patients with PBC that had Sjogrens syndrome. At the time of the previous study, data was not yet available regarding patients with PBC without sicca complaints. Therefore, to investigate the extent of salivary gland involvement in PBC, we collected lip biopsy sections from 9 PBC patients diagnosed as PBC by liver biopsy, without clinical or histologic features of Sjogrens syndrome and 9 PBC patients with established Sjogrens syndrome. Using immunohistochemical staining with both a murine monoclonal antibody. C355.1, and a human combinatorial antibody, SP4, we examined the ducts of these salivary glands for the presence of the characteristic aberrant staining pattern found in patients with PBC. We report that 6/9 PBC patients fulfilling established Sjogrens syndrome criteria and 6/9 PBC patients lacking features of Sjogrens syndrome showed intense staining of the ductal epithelial cells of the salivary gland. These data suggest that the PBC-specific antigen recognized by C355.1 and SP4 in bile duct epithelial cells is expressed aberrantly in the salivary gland in 66% of patients with PBC, independent of Sjogrens syndrome. This finding suggests a common disease process in these two tissues. Further, expression of this molecule may be an early marker of salivary gland involvement in patients with PBC.

Immunoreactivity of antimitochondrial autoantibodies in Japanese patients with primary biliary cirrhosis

The incidence and prevalence of primary biliary cirrhosis show wide geographic differences. The frequency of this disease in Japan is lower than in Northern Europe. To elucidate the immunoreactivity of serum with enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) and the M2 mitochondrial antigenic complex in Japanese patients, we examined sera from 107 patients with primary biliary cirrhosis from three geographically different regions of Japan. The sera were assayed by immunofluorescence on frozen tissue sections, immunoblotting on bovine heart mitochondria and recombinant E2 subunit of branched chain oxo-acid dehydrogenase complex (BCOADCE2), ELISA using recombinant E2 subunit of human pyruvate dehydrogenase complex (PDC-E2) and purified porcine 2-oxoglutarate dehydrogenase complex (OGDC), and enzyme inhibition assay using porcine PDC and OGDC. Of the 107 sera, 95 (88%) reacted by immunofluorescence, 102 (95%) by immunoblotting with at least one of the M2 autoantigens, although only 78 (73%) reacted with PDC-E2; 72 (67%) by ELISA with PDC-E2; and 81 (76%) with PDC by the enzyme inhibition assay. Thus, the frequency of reactivity with PDC-E2 by all assays was lower for Japanese than the reported frequency for Caucasian patients with primary biliary cirrhosis, whereas the frequency of reactivity by immunoblotting and ELISA against 2-OADC enzymes other than PDC was relatively higher. The relative frequency of reactivity of autoantibodies to the M2 autoantigens was similar for the three different regions of Japan. The different autoantibody profiles for Japanese and Caucasian patients with primary biliary cirrhosis point to immunogenetic and environmental determinants of this disease, which should provide new insights into its autoimmune origins.

A case of posttransfusion Hepatitis A

SummaryA 63-year-old female case of cancer of the colon who developed posttransfusion hepatitis A was presented. She became ill 49 days after receiving a single unit of concentrated red cells from a donor who also developed hepatitis A 10 days after donation.

Ursodeoxycholic acid inhibits histamine release from rat peritoneal mast cells

Abstract Although the immunomodulatory properties of ursodeoxycholic acid (UDCA) have been well documented, the effects of UDCA on mast cell function are unknown. The aim of the present study was to investigate in vitro the effects of UDCA on histamine release from mast cells induced by a hydrophobic bile acid (i.e. chenodeoxycholic acid) and by classical mast cell activators (i.e. compound 48/80 and concanavalin A). We incubated 5 × 10 5 purified rat peritoneal mast cells with the aforementioned agents in the presence or absence of UDCA and assessed the extent of mast cell activation by quantitating the release of histamine, a prototypic mast cell-derived mediator. UDCA dose-dependently inhibited histamine release from mast cells induced by chenodeoxycholic acid, compound 48/80, and concanavalin A. Our in vitro data suggest a hitherto unrecognized, inhibitory action of UDCA on histamine release from mast cells and a potential benefit of UDCA for mast cell-related disorders.

Clinical features of fulminant hepatitis: An etiological analysis.

当教室にて1981年から1993年までの13年間に経験した劇症肝炎40例を対象に,輸血スクリーニング法の確立した時期を考慮して,1989年以前と1990年以降に分けてその成因を比較し,成因ウイルス別にみた臨床像を検討した.成因は,ウイルス性35例,薬剤性1例,自己免疫性4例であり,ウイルスの重感染例は認めなかった.1989年以前はB型68%(輸血後例44%),N型16%であったが,1990年以降はB型20%(輸血後例0%),N型47%とB型の明らかな減少とN型の増加傾向を認めた.C型の臨床像はB型に比して,1)肝炎発生から脳症発現までの期間が長い,2)脳症発現時の総ビリルビン値が高い一方,PT(%)が比較的保たれている,3)血清トランスアミナーゼの低下が遷延している,4) AFPの反応が低い,などの特徴を認めた.N型はB型とC型の中間の臨床像を呈しており,その成因については今後さらに検討が必要と考えられた.

Aberrations of tumor suppressor p53 gene and retinoblastoma gene in two cases of hepatocellular carcinoma associated with primary biliary cirrhosis

Abstract We report two autopsy cases of hepatocellular carcinoma (HCC) associated with primary biliary cirrhosis (PBC) in which there were no serological markers for hepatitis B or C virus infection, and which have focused our attention on aberrations of the tumor suppressor p53 gene and the retinoblastoma (Rb) gene. In one of the cases, there was loss of heterozygosity (LOH) and a missense mutation of p53 (G to A point mutation in codon 244); while in the other case, there was LOH of the Rb gene. It was concluded that there are distinct aberrations in either p53 or Rb in HCC associated with PBC, the same as in HCC associated with viral hepatitis, although it remains unclear whether there is a p53 mutation hot spot in HCC associated with PBC, as in aflatoxin-related HCC. This is the first genetic study on aberrations of tumor suppressor genes in HCC associated with PBC.