Shingo Miyaguchi

A randomized, controlled trial of weekly administration of lymphoblastoid interferon in patients with chronic hepatitis C

To evaluate the efficacy of a treatment of weekly interferon administration in patients with chronic hepatitis C, 36 patients were randomly assigned to two groups. In one group lymphoblastoid interferon was given at a dose of 6 million units, intramuscularly, once per week for 24 weeks, and no treatment was given to the other. Serum alanine aminotransferase levels in the treated group were significantly lower during therapy than in the control group, although there was no significant difference between these two groups before therapy. The normalization of serum alanine aminotransferase levels at the end of therapy was observed in 50% of the treated group, and in 11.1% of the control group. This difference was statistically significant (p < 0.03). Response to interferon was better in patients with chronic persistent hepatitis or with chronic active hepatitis than in patients with chronic active hepatitis with cirrhosis. Relapse after the end of therapy was observed in 83.3% of the responders. These results indicate that the weekly administration of 6 million units of lymphoblastoid interferon is effective in decreasing serum alanine aminotransferase levels in patients with type C chronic persistent hepatitis or chronic active hepatitis.

Fatal herpes simplex hepatitis type 2 in a post-thymectomized adult

SummaryThe authors report an unusual case of herpes simplex type 2 (HSV) hepatitis which presented as part of a systemic HSV infection accompanied by disseminated intravascular coagulation (DIC). The patient was a 49-year-old Japanese male who three months prior to admission underwent surgical resection of his thymus for an invasive thymoma. Postoperatively, he received a course of chemotherapy which included prednisone, cyclophosphamide, vincristine, and pinorubicin. After discharge from the hospital, he was put on a maintenance dosage of prednisone and cyclophosphamide. Two weeks prior to this admission, the patient developed rhinorrhea, chills and general fatigue. Routine follow-up laboratory tests revealed markedly elevated liver enzymes which led to his immediate hospitalization. The tentative diagnosis on admission was fulminant hepatitis with DIC. The patient’s condition steadily worsened during his hospitalization and acyclovir was initiated on the 4th hospital day due to the possibility of HSV hepatitis. He died on the same day. Histopathology performed on the liver at autopsy revealed hepatic inclusion bodies of HSV with positive immunohistochemical detection of the HSV type 2 antigen. Our case is the first report of HSV hepatitis associated with the removal of the thymus secondary to thymoma. It supports previous observations of disseminated HSV infection being prevalent in those patients with disorders of cell mediated immunity.

Elevation of serum eosinophil cationic protein in primary biliary cirrhosis

Abstract It has recently been reported that in patients with primary biliary cirrhosis (PBC), eosinophils are not only increased in the peripheral blood, but also infiltrted in the liver portal tracts. There is general agreement that eosinophils and eosinophil cationic protein (ECP) released from eosinophils contribute to cellular damage, particularly in allergic inflammation. In the present study, ECP was measured by the radioimmunoassay in sera of patients with a variety of liver diseases including PBC. Serum ECP levels were significantly higher in patients with PBC than in those with chronic viral hepatitis, in those with liver cirrhosis, and in healthy subjects. There were no significant differences in serum ECP levels between symptomatic and asymptomatic PBC. The present study suggests that high levels of serum ECP may reflect high grades of eosinophil infiltration around the septal and interlobular bile ducts characterized by chronic non-suppurative destructive cholangitis, particularly in the early stages of PBC.

A case of parathyroid hormone-related peptide producing gallbladder carcinoma and establishment of a cell line, PTHrP-GBK.

Hypercalcemia is sometimes associated with patients bearing malignant tumors. Local osteolytic hypercalcemia (LOH) due to bone metastasis of malignancy is one of the causes of hypercalcemia, while another main cause that has been documented is humoral hypercalcemia of malignancy (HHM). Parathyroid hormone-related peptide (PTHrP) has been described as the main underlying substance that causes HHM. In this report, we describe a female patient with gallbladder carcinoma and marked hypercalcemia of malignancy. Additionally, she is the first source for the establishment of a cell line from the original resected tissue.

Immunohistochemical characterization of hepatic eosinophil cationic protein in primary biliary cirrhosis

Abstract We have previously reported that serum eosinophil cationic protein (ECP_ levels are increased in primary biliary cirrhosis (PBC). However, little is known about the role of eosinophils in the pathogenesis of this disease. In this study, liver biopsy specimens obtained from 27 PBC patients (stage I: 11 cases; stage II: 9 cases; stage III: 5 cases; stage IV: 2 cases) were stained with a monoclonal antibody (EG2) produced against ECP in an attempt to elucidate whether EG2-positive eosinophils are involved in the destruction of bile duct in PBC. Needle liver biopsy specimens obtained from 24 patients with chronic hepatitis C (CHC) were used as controls. In PBC, more than 10 EG2-positive cells were noted per portal tract in 6 cases, less than 10 EG2-positive cells in 10 cases and none in 11 cases. In CHC, more than 10 EG2-positive cells were detected per portal tract in only one case, less than 10 EG2-positive cells in 3 cases and none in 20 cases. According to the semi-morphometric statistical analysis, the hepatic infiltration rate of EG2-positive activated eosinophils into the portal tract was significantly higher in PBC than in CHC. Based on the stages of PBC, the infiltration rate of EG2-positive cells was significantly higher in stages I and II than in stages III and IV. A significant correlation was found between EG2-positive cell infiltration and small round cell infiltration. These findings suggest that EG2-positive, activated eosinophils may be involved in the early stages of PBC when the inflammatory changes are localized in the portal tract. It is tentatively speculated that activated eosinophils may play a role possibly as effector cells in the immunopathogenesis of PBC.

Elevated plasma RANTES in primary biliary cirrhosis patients

Abstract RANTES (regulated on activation, normal T cell expressed and secreted) is a member of a large supergene family of proinflammatory cytokines called C-C chemokines and it is expressed by T lymphocytes, fibroblasts, endothelial cells, platelets, mesangial cells, and renal tubular epithelial cells. RANTES is chemotactic for eosinophils, basophils, monocytes/ macrophages, and CD4 + memory T cells. This chemokine plays an important role in allergic inflammation and autoimmune responses in a variety of diseases, such as asthma and rheumatoid arthritis. However, there have been few studies on RANTES in liver disease. In an attempt to assess the relationships between plasma RANTES levels and the stages of primary biliary cirrhosis (PBC), the present study was designed to measure plasma RANTES levels in plasma by the ELISA in patients with PBC and chronic hepatitis C (CHC) and liver cirrhosis (LC) and in healthy subjects. Plasma RANTES levels in patients with PBC were significantly higher than in those with LC and in healthy subjects. They were also significantly higher in stages I and II of PBC (group A) than in stages III and IV of PBC (group B). There was a significant correlation between peripheral eosinophil counts and plasma RANTES levels. A significant correlation was also noted between the grade of eosinophil infiltration and the plasma RANTES levels. It was concluded RANTES plays an important role in the early stages of PBC.

Changes in high mannose-type glycoproteins of peripheral blood mononuclear cells in cirrhosis patients

Abstract Glycoproteins of peripheral blood mononuclear cells (PBMC) in patients with liver cirrhosis (LC) have not yet been studied. In the present study, we investigated high mannose-type glycoproteins of PBMC from patients with LC. We showed that [2- 3 H]mannose uptake by PBMC and binding of glycoproteins from PBMC to concanavalin A (Con A)-Sepharose were significantly lower in patients with LC than in healthy subjects. These results indicate that high mannose-type glycoproteins of PBMC are decreased in patients with LC. High mannose-type glycoproteins play an important role in the formation of functional high-affinity interleukin-2 (IL-2) receptors. Thus, the decrease of high mannose-type glycoproteins may be one of the factors affecting the function of T or natural killer (NK) cells, which require IL-2 receptors to exert various immunological functions, in patients with LC.

Treatment of chronic hepatitis C with weekly administration of interferon-α

SummaryTo evaluate the efficacy of weekly administration of interferon (IFN)-α, we studied 23 anti-HCV positive patients with chronic hepatitis diagnosed by liver needle biopsy. Thirteen patients received weekly intramuscular injections of 6 MU human lymphoblastoid interferon (HLBI) for 24 weeks, and the other 10 patients were given no treatment. We examined liver-specific idiotype-bearing antibody (LSIA) in the patients’ sera. This HLBI treatment was easily tolerated by all the treated patients. In the treated group serum alanine aminotransferase (ALT) level significantly decreased during HLBI treatment. Normalization of serum ALT level by the end of treatment was observed in 7/13 (54% ) of the treated patients but in 0% of the non-treated patients. Anti-HCV was detectable in all the patients during the treatment. Those who had high LSIA levels did not respond to HLBI treatment. These results demonstrate that weekly administration of IFN is sufficient to suppress disease activity in patients with chronic hepatitis C and that patients with high LSIA levels are unlikely to respond to IFN therapy.