Severe lipodystrophy is characterized by diminished adipose tissue and hypolep tinemia, leading to ectopic triglyceride accumulation.In the liver, this is asso ciated with steatosis,potentially leading to nonalcoholic...Severe lipodystrophy is characterized by diminished adipose tissue and hypolep tinemia, leading to ectopic triglyceride accumulation.In the liver, this is asso ciated with steatosis,potentially leading to nonalcoholic steatohepatitis (NASH) . We investigated the prevalence of NASH and the effect of leptin replacement in these patients. Ten patients with either generalized lipody strophy (8 patients ) or Dunnigan’s partial lipody strophy(2 patients) were included in this analys is. Paired liver biopsy specimens were obtained at baseline and after treatment with recombinant methionyl human leptin (r-metHuLeptin), mean duration 6.6 mont hs. The extents of portal and parenchymal in-flammation, steatosis, ballooning, presence of Mallory bodies,and fibrosis in liver biopsy specimens were scored u sing a previously validated system developed to assess NASH activity.Histologica l disease activity was defined as the sum of ballooning, steatosis, and parenchy mal inflammation scores. We concurrently tested serum triglycerides and aminotra nsferases and estimations of liver volume and fat content by magnetic resonance imaging. Eight of 10 patients met histological criteria for NASH at baseline. Af ter treatment with r-metHuLeptin,repeat histological examinations showed signif icant improvements in steatosis (P = .006) and ballooning injury (P = .005),with a reduction of mean NASH activity by 60%(P = .002).Fibrosis was unchanged. Significant re ductions were seen in mean seru- m triglycerides (1206→226mg/dL, P = .002),glucose(220→144 mg/dL, P = .02), i nsulin (46.4→24.8 μIU/mL, P =.004), ALT (54→24U/L, P = .02), AST (47→22 U/L, P = .046),liver volume (3209→2391 cm3, P = .007), and liver fat content(31→11 %, P = .006). In conclusion, r-metHuLeptin therapy significantly reduced trigl ycerides, transaminases, hepatom- egaly,and liver fat content. These reductions were associated with significant reductions in steatosis and the hepatocellular ballooning injury seen in NASH.展开更多
文摘Severe lipodystrophy is characterized by diminished adipose tissue and hypolep tinemia, leading to ectopic triglyceride accumulation.In the liver, this is asso ciated with steatosis,potentially leading to nonalcoholic steatohepatitis (NASH) . We investigated the prevalence of NASH and the effect of leptin replacement in these patients. Ten patients with either generalized lipody strophy (8 patients ) or Dunnigan’s partial lipody strophy(2 patients) were included in this analys is. Paired liver biopsy specimens were obtained at baseline and after treatment with recombinant methionyl human leptin (r-metHuLeptin), mean duration 6.6 mont hs. The extents of portal and parenchymal in-flammation, steatosis, ballooning, presence of Mallory bodies,and fibrosis in liver biopsy specimens were scored u sing a previously validated system developed to assess NASH activity.Histologica l disease activity was defined as the sum of ballooning, steatosis, and parenchy mal inflammation scores. We concurrently tested serum triglycerides and aminotra nsferases and estimations of liver volume and fat content by magnetic resonance imaging. Eight of 10 patients met histological criteria for NASH at baseline. Af ter treatment with r-metHuLeptin,repeat histological examinations showed signif icant improvements in steatosis (P = .006) and ballooning injury (P = .005),with a reduction of mean NASH activity by 60%(P = .002).Fibrosis was unchanged. Significant re ductions were seen in mean seru- m triglycerides (1206→226mg/dL, P = .002),glucose(220→144 mg/dL, P = .02), i nsulin (46.4→24.8 μIU/mL, P =.004), ALT (54→24U/L, P = .02), AST (47→22 U/L, P = .046),liver volume (3209→2391 cm3, P = .007), and liver fat content(31→11 %, P = .006). In conclusion, r-metHuLeptin therapy significantly reduced trigl ycerides, transaminases, hepatom- egaly,and liver fat content. These reductions were associated with significant reductions in steatosis and the hepatocellular ballooning injury seen in NASH.
