The incidence of hepatocellular carcinoma was lower in patients with sustained response to interferon therapy than historical controls and nonresponders. Interferon therapy may decrease the risk for hepatocellular carcinoma in patients with chronic hepatitis C.

Familial hypokalemic periodic paralysis is an autosomal dominant genetic muscle disease characterized by periodic attacks of muscle weakness associated with a decrease in serum potassium. There are two major missense mutation sites in the calcium channel 1 subunit (CACNA1S) gene in these patients. We recently encountered a 13-year-old Japanese boy who had collapsed following exercise and was found to have a low serum potassium level. Clinical and genetic studies including exploration of his family tree proved that he and his maternal relatives had the disease with the missense mutation, Arg528His (CGC CAC). However, his mother and grandmother had no symptoms of the disease, indicating reduced penetrance in female carriers. Sexual difference in the penetrance of this disease and the association between the clinical symptoms and the types of genetic defects are discussed. (Internal Medicine 43: 218-222, 2004)

We have noticed that functional disorders of the liver characterized by hepatomegaly and an increase in serum gamma-glutamyl transpeptidase develop in patients with prostatic cancer who are placed under longterm therapy with massive doses of estrogen after castration. We performed laparoscopy in six cases of prostatic cancer with hepatomegaly so that we could study the morphology of the liver. Our findings were as follows. In five, the histological features of the liver biopsies were very similar to those seen in alcoholic hepatitis. In spite of this fact, two of the five had no history of alcohol consumption. Furthermore, in one other case, liver damage resembling alcoholic hepatitis developed during abstinence. The findings in these three cases suggested that long-term, massive doses of synthetic estrogen may lead to liver injury similar to alcoholic hepatitis in nonalcoholics. The ultrastructural findings of the liver cells were also suggestive of the adverse effect of treatment. All cases were negative for hepatitis B surface antigen. Recent reports have demonstrated some nonalcoholics with histological features of the liver indicative of alcoholic hepatitis. This particular condition was termed "nonalcoholic steatohepatitis" by Ludwig et al. It is quite likely that synthetic estrogen is also responsible for "nonalcoholic steatohepatitis" when it is used in massive doses.

The patients with HCV-positive BR were virologically different from those with CR, and had lower ALT levels and histologic activity when compared to those with CR and NR.

The relationship between the changes in the amount of the components of the liver microsomal electron transport systems and drug hydroxylase activities on administration of p-nitroanisole was investigated. The content of cytochrome P-450 in the p-nitroanisole-treated rats was not significantly different from that in the controls during the treatment. The cytochrome b5 content increased 2.2-fold over that of the controls after 14 days of treatment. Demethylation activities per mg microsomal protein of p-nitroanisole, aminopyrine, and benzphetamine were enhanced 2.7-, 2.4-, and 2.8-fold, respectively, but aniline hydroxylase activity was not enhanced. Similar results were obtained with microsomes from diisopropyl 1,3-dithiol-2-ylidenemalonate (NKK-105)-treated rats. The time-course study of changes in the amount of the components of drug hydroxylase systems suggested that the increase in cytochrome b5 content enhanced the demethylation activities. In the reconstituted system containing cytochrome P-450 partially purified from p-nitroanisole- or NKK-105-treated rats, cytochrome b5 was required for the maximal activities of the demethylation reactions, but did not participate in aniline hydroxylation. These findings showed good correlation between the change of cytochrome b5 content and the demethylation activities and suggested that the increase in cytochrome b5 content might enhance the demethylation activity by stimulating supply of a second electron to cytochrome P-450.