Takayoshi Fukutomi

Decline of hepatitis C virus load in serum during the first 24 h after administration of interferon-beta as a predictor of the efficacy of therapy

BACKGROUND/AIMS Hepatitis C virus (HCV) kinetics during interferon (IFN)-alpha treatment have been evaluated recently, however, little is known about the resultant viral kinetics in IFN-beta treatment. In this study, we evaluated HCV kinetics during the first 24 h of IFN-beta treatment, and also assessed their relationship to therapeutic outcomes. METHODS We measured HCV RNA levels at 0 and 24 h after the initiation of IFN-beta treatment, and we calculated the decay slope, viral half-life, and viral production and clearance. Then we analyzed these factors as they related to therapeutic responses with IFN-beta as well as to clinical variables, i.e. genotype, diversity of hyper variable region, and histological findings. RESULTS Patients with sustained responses (SR) displayed steeper decay slopes of the viral load than those without SR (2.87 +/- 1.41 vs. 1.82 +/- 1.66, P = 0.031). On the other hand, the decay slope was not affected by the clinical variables. The values of viral half-life and viral production and clearance showed no significant correlation to the response and the clinical variables. CONCLUSION This study demonstrated that the decay slope of the viral load during the first 24 h is related to the virological response to IFN-beta treatment.

Thermolabile β-2 macroglycoprotein (Hakata antigen) in liver disease: biochemical and immunohistochemical study

Abstract Thermolabile β-2 macroglycoprotein is a novel serum protein that was detected by an autoantibody in sera of a Japanese woman with systemic lupus erythematosus. We developed an enzyme-linked immunosorbent assay for this glycoprotein and measured its serum levels in patients with chronic liver disease. There were significant correlations between serum levels of this glycoprotein and those of albumin and cholinesterase. The serum levels of TLβ2MG decreased with increasing severity of cirrhosis. Immunohistochemical staining using monoclonal anti-thermolabile β-2 macroglycoprotein antibody revealed positive staining in the cytoplasm of the hepatocytes. These data strongly suggested that hepatocyte may be one of the production sites of this glycoprotein. Measurement of serum levels of this glycoprotein was useful for evaluation of hepatic function in chronic liver disease.

Long-term prognosis and prognostic factors of liver cirrhosis in the 1980s

Abstract The prognosis of 174 patients with cirrhosis during the 1980s (1981–89) was analysed. The estimated survival rates were 87.3% in 3 years and 68.5% in 5 years. During the follow‐up period, 58 patients died: 20 of hepatocellular carcinoma (37.7%); 11 of hepatic failure (20.8%); eight of gastrointestinal bleeding (15.1%); and 14 of other causes (26.4%). Multivariate analysis revealed that serum albumin, indocyanine green retention rate at 15 min and white blood cell count were significantly associated with prognosis. The results were also compared to our previous study covering the 1970s (1971–80). The estimated survival rate was significantly improved compared to that during the 1970s (54.3% in 5 years, P < 0.001). In the 1980s, hepatic failure mortality significantly decreased (P < 0.01), and non‐liver‐related mortality significantly increased (P < 0.05). In summary, the prognosis of cirrhosis has improved in recent years, and changes of death cause and prognostic factors were observed. It was concluded that to evaluate the severity and prognosis of cirrhosis, new indices and appropriate classification were necessary.

Oral contraceptive-dependent growth of focal nodular hyperplasia

Abstract A 22 year old woman was incidentally found to have a hepatic small haemangioma‐like mass, measuring 1.4 cm in diameter, by an ultrasonographic examination. The mass demonstrated no change in size or appearance for 6 months until the patient began to take oral contraceptives. Eventually, the mass increased to 2.0 cm in diameter after using oral contraceptives for 6 months. A histological examination suggested the mass to be typical focal nodular hyperplasia, and not hepatic adenoma. There was no further change in either size or appearance in the ensuing 1 year after the discontinuation of oral contraceptives.

Clinical significance of the serum levels of the 7S domain of type IV collagen in patients with primary biliary cirrhosis

The serum levels of the 7S domain of type IV collagen were measured with a radio‐immunoassay in 42 patients with primary biliary cirrhosis (asymptomatic: n= 28; symptomatic: n= 14), 10 patients with chronic active hepatitis, 10 patients with liver cirrhosis and 10 healthy female controls. Serum levels of the 7S domain of type IV collagen were: 4.28 ng/mL (3.88–4.72 ng/mL; mean and range of mean ± s.d.) in healthy controls; 5.97 ng/mL (5.07–7.02 ng/mL) in patients with chronic active hepatitis; 8.23 ng/mL (6.40–10.58 ng/mL) in patients with liver cirrhosis; and 6.79 ng/mL (4.76–9.67 ng/mL) in patients with primary biliary cirrhosis. Patients with liver cirrhosis and primary biliary cirrhosis had higher levels of serum 7S domain of type IV collagen than healthy controls (P < 0.001, respectively). Serum levels of the 7S domain of type IV collagen in patients with asymptomatic primary biliary cirrhosis, 5.83 ng/mL (4.55–7.48 ng/mL) were significantly lower than those in symptomatic primary biliary cirrhosis, 9.18 ng/mL (6.53–12.91 ng/mL; P<0.001). Serum levels of the 7S domain of type IV collagen increased significantly along with advancement of the histological stages of primary biliary cirrhosis. Serum levels of the 7S domain of type IV collagen in the paired sera of eight patients with asymptomatic primary biliary cirrhosis (mean interval 30 months, range 12–48 months) showed significant rises during the intervals (P < 0.05), while serum levels of albumin and total bilirubin did not change significantly during these intervals. It is concluded that serum levels of the 7S domain of type IV collagen were good markers of fibrosis and may be useful for evaluation of the clinical status in the patients with primary biliary cirrhosis.

Kinetics of the hepatitis C virus during interferon therapy as a marker of therapeutic response

Background: The viral load and subtype of hepatitis C virus (HCV) are predictors of the efficacy of interferon (IFN) therapy. The kinetics of HCV during IFN therapy have been described recently, suggesting that HCV infection is highly dynamic. These observations have raised the issue as to whether early monitoring of the viral load can help guide IFN therapy.

Case report : Primary splenic non-Hodgkin's B cell lymphoma in a patient with chronic hepatitis C

A case of primary splenic lymphoma in a patient with chronic hepatitis C is reported. A 69‐year‐old man with chronic hepatitis C was admitted to Fukuoka City Hospital for evaluation of an enlarging splenic tumour. In the spleen, ultrasonographic examination revealed a hypoechoic tumour and computed tomography demonstrated a non‐enhancing low density area measuring 7 cm in diameter; coeliac angiography revealed a hypovascular tumour. Gallium scintigraphy showed uptake of the radioisotope in the splenic tumour. A splenectomy was performed and the morphological and immunohistochemical findings of this tumour were compatible with those of non‐Hodgins B cell lymphoma. Recently, cases of malignant B cell lymphoma associated with hepatitis C virus infection have been reported. Lymphotropism of hepatitis C virus may play a pathological role in the development of non‐Hodgkins lymphoma. We emphasize the importance of considering lymphoma in the differential diagnosis of extrahepatic disorders during the course of chronic hepatitis C virus infections.

Rise of plasma myeloperoxidase during interferon therapy

Abstract The plasma myeloperoxidase (MPO) level was evaluated using a specific radio‐immunoassay (RIA) for MPO in α2b‐interferon (IFN)‐treated patients with chronic viral hepatitis. The plasma MPO was checked before and after the initial 2 weeks use of IFN at a dose of 6 × 106 U/day. The mean concentration of plasma MPO was found to be markedly higher after IFN therapy than that before the therapy (421.7 ± 34.3 vs 242.9 ± 23.0 ng/mL, P < 0.001). The plasma MPO negatively correlated with the granulocyte count (r= ‐0.37, P < 0.02) and the platelet count (r= 0.49, P < 0.01), while it positively correlated with serum alkaline phosphatase (ALP; r= 0.41, P < 0.03). The plasma MPO also showed a strong correlation with plasma polymorphonuclear granulocyte elastase (PMN elastase; r= 0.73, P < 0.001). Our study thus suggests that the increased release of MPO from destroyed granulocytes is responsible for the high concentrations of the plasma MPO in patients during IFN therapy, because the plasma MPO, PMN elastase and ALP abundant in granulocytes all increased in spite of a decrease in the granulocyte count. Granulocytopenia during IFN therapy may therefore be due to the increased destruction of granulocytes in addition to a direct suppression of the bone marrow by IFN.