Yasuhiro Kato

Tocilizumab (TCZ) is an interleukin-6 (IL-6) inhibitor used for the treatment of rheumatoid arthritis (RA). It was developed in 2008, and its effectiveness is supported by evidence from all over the world based on its first decade of use. Although the overall efficacy and safety profiles of TCZ are similar to those of tumor necrosis factor (TNF) inhibitors, TCZ displays certain differences. The most notable advantage of TCZ is its usefulness as a monotherapy. Additionally, TCZ is favorable in the improvement of systemic inflammatory symptoms such as anemia and fatigue. The low immunogenicity of TCZ contributes favorably to long-term drug retention. Due to frequent relapse after TCZ cessation, TCZ use should be tapered beyond remission. During TCZ therapy, C-reactive protein (CRP) is unable to recognize disease activity and the severity of infection. The most common adverse events (AEs) are infection and abnormalities in laboratory findings including dyslipidemia, neutropenia, thrombocytopenia, and abnormality of liver enzymes. TCZ obscures the symptoms of infection. Therefore, stealth infections without obvious CRP elevation can sometimes cause severe damage to patients. Lower intestinal perforation is an uncommon but serious AE in TCZ therapy. Further clinical investigations will continue to refine the IL-6 inhibitory strategy.

The value of various screening methods in the detection of early hepatocellular carcinoma was investigated in 95 patients with cirrhosis. Infusion hepatic angiography and computed tomography with angiography were performed yearly, ultrasound every 3 months, and determination of serum alpha-fetoprotein levels every 2 months. "Space-occupying lesions" suspicious for hepatocellular carcinoma were found in 13 of the 95 cases (13.7%). Detection rates of "space-occupying lesions" were 77% for infusion hepatic angiography, 77% for computed tomography with angiography and 54% for ultrasonography, respectively. In 8 of the 13 cases, "space-occupying lesions" were subsequently confirmed as hepatocellular carcinoma by operative findings or clinical course. Serum alpha-fetoprotein levels were negative in 3 of the 8 hepatocellular carcinoma-confirmed cases, and 3 of the remaining 5 cases demonstrated levels above 400 ng per ml at the time of diagnosis. A radical resection of hepatocellular carcinoma was successfully performed in two cases. Although it was difficult to differentiate hepatocellular carcinoma from other lesions in the case of "space-occupying lesions" smaller than 2 cm in diameter, the results suggest that regularly scheduled screening may be useful to detect early hepatocellular carcinoma.

The apoptotic cell death induced in D-galactosamine-sensitized mice by administration of lipopolysaccharide was characterized. Administration of lipopolysaccharide caused apoptotic cell death in livers of D-galactosamine-sensitized mice. Apoptotic cells were also detected in the kidney, thymus, spleen, and lymph node. Severe hepatic apoptosis in D-galactosamine-sensitized mice was reproduced by transfer of the sera from mice injected with D-galactosamine and lipopolysaccharide. The hepatocyte apoptosis induced by lipopolysaccharide was completely prevented by an anti-tumor necrosis factor alpha antibody but not by an anti-gamma interferon antibody. Administration of recombinant tumor necrosis factor into D-galactosamine-sensitized mice also caused hepatocyte apoptosis. Lipopolysaccharide-induced hepatocyte apoptosis in D-galactosamine-sensitized mice did not seem to be mediated by Fas antigen. It was suggested that lipopolysaccharide- induced hepatic injury and failure in D-galactosamine-sensitized mice was due to the apoptotic cell death of hepatocytes caused by tumor necrosis factor alpha released in the circulation.