Ryoichi Okamoto

Cytokine profile in the liver of primary biliary cirrhosis.

We characterized the cytokine profile in the liver of patients with primary biliary cirrhosis (PBC). Total RNA was extracted from the biopsy specimens of 9 patients with early-stage PBC, 10 with chronic hepatitis C (CHC), and 4 normal controls. cDNA was prepared and amplified with a polymerase chain reaction using primers for interferon (IFN)-γ and interleukin (IL)-2, -4, -5, -6, -10, -12 (p40), and -15. Cytokines such as IFN-γ and IL-5, -6, -10, -12, and -15 were expressed in most cases of PBC. Expression rates of IL-5 and IL-6 were higher than in CHC and controls. The higher expression rate of IL-5 in PBC was associated with eosinophil infiltration. IL-2 and IL-4 were rarely detected. Semiquantitative analysis revealed that the expression of IFN-γ and IL-10 was reversed in PBC and CHC: high IFN-γ and low IL-10 in PBC and high IL-10 and low IFN-γ in CHC. These results suggest that cytokine expression is skewed in PBC and both Th1 and Th2 cytokines may play a role in the pathogenesis.

Cost‐effectiveness of the surveillance program of hepatocellular carcinoma depends on the medical circumstances

Background and Aim:  The clinical features of hepatocellular carcinoma (HCC) and the medical environment are diverse in different geographic areas. The aim of this study is to evaluate the cost‐effectiveness of the surveillance of HCC in different medical circumstances.

A scoring system for primary biliary cirrhosis and its application for variant forms of autoimmune liver disease

Background: Although primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) are two independent autoimmune liver diseases, it is sometimes difficult to characterize the variant forms of autoimmune liver disease. A PBC scoring system, in combination with the AIH scoring system may be helpful to characterize such patients. Methods: A PBC scoring system was introduced that selected 14 categories characteristic of PBC. One hundred and thirty-four patients with PBC, 31 patients with autoimmune cholangitis (AIC), 22 patients with overlap syndrome, and 48 patients with AIH were included in the study. The AIC patients fulfilled the PBC criteria but were negative for anti-mitochondrial antibody and positive for anti-nuclear antibody. Overlap syndrome patients fulfilled both the PBC and AIH criteria. Results: The total scores (means ± SD) for the PBC, AIC, overlap syndrome, and AIH patients were 23.3 ± 4.7, 9.3 ± 4.4, 18.0 ± 5.9, and 3.6 ± 3.3, respectively. When definite and probable PBC patients were defined as those with a total score of over 17 and 9–17, respectively, all except for 1 patient could be classified as definite or probable PBC. Four of the 48 AIH patients were classified as probable PBC. PBC scores for the variant autoimmune liver diseases showed a wide deviation. Plotting both PBC and AIH scores in a rectangular coordinate enabled us to locate each patient with variant forms according to the deviation from classical PBC or AIH. Conclusions: The PBC scoring system might be useful in characterizing the features of variant forms of autoimmune liver disease.

Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis

Aim:  In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3‐positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians.

Prediction of the ablated area by the spread of microbubbles during radiofrequency ablation of hepatocellular carcinoma

Abstract: Background/Aim: Radiofrequency ablation (RFA) is effective for the treatment of hepatocellular carcinoma (HCC). To prevent the ablation of adjacent organs and vessels, the spread of microbubbles generated by heating during RFA was observed by ultrasonography (US) and used to predict the ablated area; however, several reports documented that discrepancies existed between the spread of microbubbles and the ablated area.

Expression of Perforin and Fas Ligand mRNA in the Liver of Viral Hepatitis

Cytotoxic T lymphocytes (CTLs) play an important role in the pathogenesis of viral hepatitis. We studied the expression of mRNAs of perforin and Fas ligand (Fas-L) in biopsy specimens from chronic hepatitis B (CHB) (15 cases) and hepatitis C (CHC) patients (13 cases). Both perforin and Fas-L mRNAs were detected in all cases of both CHB and CHC. No messages were detected in the control livers from two cases of fatty liver, a case of Gilberts syndrome, and a case of Dubin–Johnson syndrome. Semiquantitative analysis revealed a positive correlation between the intensity of perforin and Fas-L mRNAs in both CHB and CHC. In CHB, the intensity of both perforin and Fas-L mRNAs showed a positive correlation with the histological activity and serum alanine aminotransferase level, while the correlation was not apparent in CHC. These results suggest that both perforin and Fas/Fas-L systems are involved in the pathogenesis of liver cell injury of CHB and CHC.

Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis

Aim:  Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20–30% of patients are negative for ANA. We assessed the clinical features of ANA‐negative patients.

High frequency of circulating HBcAg-specific CD8 T cells in hepatitis B infection: a flow cytometric analysis

Viral antigen‐specific T cells are important for virus elimination. We studied the hepatitis B virus (HBV)‐specific T cell response using flow cytometry. Three phases of HBV infection were studied: Group A, HBeAg (+) chronic hepatitis; Group B, HBeAb (+) HBV carrier after seroconversion; and Group C, HBsAb (+) phase. Peripheral T cells were incubated with recombinant HB core antigen (HBcAg), and intracytoplasmic cytokines were analysed by flow cytometry. HBcAg‐specific CD4 and CD8 T cells were identified in all three groups and the number of IFN‐γ‐positive T cells was greater than TNF‐α‐positive T cells. The frequency of IFN‐γ‐positive CD4 and CD8 T cells was highest in Group C, compared with Groups A and B. No significant difference in the HBcAg‐specific T cell response was observed between Group A and Group B. The HBcAg‐specific CD8 T cell response was diminished by CD4 depletion, addition of antibody against human leucocyte antigen (HLA) class I, class II or CD40L. Cytokine‐positive CD8 T cells without HBcAg stimulation were present at a high frequency (7 of 13 cases) in Group B, but were rare in other groups. HBcAg‐specific T cells can be detected at high frequency by a sensitive flow cytometric analysis, and these cells are important for controlling HBV replication.

Human leukocyte antigen DR status and clinical features in Japanese patients with type 1 autoimmune hepatitis

Aim:  Human leukocyte antigen (HLA) DR status affects the clinical features of autoimmune hepatitis. In Caucasians, patients with DR3 have poorer outcomes. In Japan, the relationship between HLA DR status and clinical features has yet to be fully examined.

Prevalence and associated factors with esophageal varices in early primary biliary cirrhosis

Background and Aims:  Recent routine testing for anti‐mitochondrial antibodies has increased the number of patients with early primary biliary cirrhosis (PBC). The prevalence and clinical significance of esophageal varices in those patients remains obscure.