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Primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), is ranked third in men and fifth in women as a cause of death from malignant neoplasms in Japan. The number of deaths and death rate of HCC began to increase sharply in 1975. These numbers peaked at 34,510 and 27.4/100,000, respectively, in 2004, but decreased to 33,662 annual deaths and a 26.7/100,000 death rate in 2006. Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are both major causes of HCC, HCV-related HCC represents 70% of all cases. The incidence of HCC without hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV) accounts for 8%-15% of HCC patients nationwide. Geographically, HCC is more frequent in western than eastern Japan, and death rates of HCC in each prefecture correlate with anti-HCV, but not HBsAg, prevalence. Interferon therapy for chronic hepatitis C reduces the risk of development of HCC, especially among patients with sustained virological response. Further research should focus on the mechanisms of carcinogenesis by HCV and HBV, development of more effective treatments, and establishment of early detection and preventative approaches. Better understanding of HCC unrelated to HCV and HBV, possibly caused by steatohepatitis and diabetes, should also be a major concern in future studies.

The long-term outcome of patients with autoimmune hepatitis (AIH) in Japan has not been well-defined. The aim of this study was to clarify the outcome of this disease over a long follow-up period compared with that of the general Japanese population as well as that among patients. A total of 203 AIH patients were enrolled for a mean follow-up period of 131 months. All patients were treated with corticosteroids with or without azathioprine. The overall survival of AIH patients was similar to that of the general population in Japan. The prognosis of AIH subgroups divided according to disease severity, sex, incidence of relapse, liver histology, presence of cirrhosis, probable or definite AIH score, antibody to hepatitis B core antigen antibody positivity, or human leukocyte antigen DR4-positivity did not differ greatly among patients. However, the prognosis of patients experiencing two or more relapses was significantly poorer than that of patients with remission or a single relapse both in univariate (P < 0.001) and multivariate (P 5 0.020) analyses. The development of liver malignancy was also a possibility among AIH patients with multiple relapses. Severe adverse effects of corticosteroids were rare, even in patients who underwent long-term treatment. Conclusion: Repeated relapses of AIH are significantly associated with a poorer longterm prognosis in Japan. AIH patients can expect a similar prognosis to that of the general population, provided they are adequately managed with continuous low doses of immunosuppressive therapy, especially after the first relapse. (HEPATOLOGY 2012;56:668-676) A utoimmune hepatitis (AIH) is an organ-specific autoimmune disease characterized by chronic inflammation of the liver, hypergammaglobulinemia, and autoantibodies.

Background Immunoglobulin (Ig) G4-associated autoimmune hepatitis (AIH) is a

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The interferon sensitivity determining region (ISDR) of the hepatitis C virus (HCV) and Thelper type 1 and type 2 (Th1/Th2) ratio were analyzed along with other host and viral factors for their ability to predict the response of patients with chronic hepatitis C to pegylated interferon alpha-2b (Peg-IFN) and ribavirin (RBV) combination therapy. A total of 120 chronic hepatitis C patients with genotype 1 HCV and high baseline viral loads who were to undergo combination therapy scheduled for 48 weeks were enrolled. Sustained virologic response (SVR) was achieved in 54 (45%) of the 120 patients. The pretreatment factors significantly associated with SVR by logistic regression analysis were ISDR mutant [odds ratio (OR) ‫؍‬ 86.0, P ‫؍‬ 0.0008], Th1/Th2 ratio < 15.5 (OR ‫؍‬ 9.6, P ‫؍‬ 0.0021), body weight 59 kg, and neutrophil count 2,300/L. A logistic regression model to estimate SVR before combination therapy was constructed using these four factors. Patients fell into three groups when plotted according to estimated and actual SVR rates: actual SVR rate was 91% (32/35) in the high sensitivity group, 41% (15/37) in the intermediate sensitivity group, and 15% (7/48) in the low sensitivity group. Rapid or early virological responses were seen in 80% of patients with high sensitivity and who achieved SVR but were found in only 40% of patients with intermediate or low sensitivity. Null-and very late virological responses were quite rare in the high sensitivity group. In conclusion, a logistic regression model that includes the sequence of ISDR of the HCV, Th1/Th2 ratio, body weight, and neutrophil count can be useful for accurately predicting actual SVR rate before combination therapy. (HEPATOLOGY 2008;48:1753-1760 C hronic infection with hepatitis C virus (HCV) can lead to chronic hepatitis and eventually liver cirrhosis and hepatocellular carcinoma. 1 Administration of antiviral agents such as interferon (IFN) can eradicate HCV in some patients with chronic hepatitis C, and the risk of complicating hepatocellular carcinoma has been reported to decrease remarkably once this is achieved. [2][3][4][5][6] HCV genotype and viral load are two major factors used to predict the response of patients with chronic hepatitis C to IFN. Patients who have genotype 1 HCV and high viral loads are relatively resistant to IFN therapy. 7 Peg-IFN and RBV combination therapy is currently the first line of therapy for these cases. 8 However, although the sustained virologic response (SVR) rate has been improved with the advent of combination therapy, it remains approximately 50%. The velocity of decrease in viral load during combination therapy is also a good indicator for predicting SVR; high SVR rates are predicted in rapid and early virological responders, whereas low SVR rates are predicted in late and nonvirological responders. [9][10][11][12] It is considered beneficial to predict the response of patients with genotype 1 HCV and high viral load to Peg-IFN and RBV combination therapy before starting treatment because therapy can be lon...

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