Hepatic ultrastructure was examined by electron microscopy in 25 patients with Gilbert's syndrome and the changes in the smooth endoplasmic reticulum quantified by grid technique. Thirteen patients showed gross hypertrophy of the smooth endoplasmic reticulum (SER). These were designated Gilbert's EM Positive. The remaining 12, designated Gilbert's EM Negative, did not differ significantly from normal controls. The EM Positive group showed a significantly greater percentage response to caloric restriction (P less than 0.01) and an exaggerated response to nicotinic acid stimulation when compared with the EM Negative group and normal controls. These results suggest that SER hypertrophy is not, as previously suggested, a constant feature of Gilbert's syndrome but rather a characteristic of a distinct subpopulation.
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