Hepatic iron has been associated with more aggressive liver disease in chronic viral hepatitis. We evaluated whether the recently described C282Y mutation of the hemochromatosis gene, designated HFE (responsible for at least 83% of hereditary hemochromatosis), was associated with more advanced liver disease in chronic hepatitis C. One hundred thirty-seven patients with biopsy-proven chronic hepatitis C were studied and liver biopsies scored for necroinflammation (grade 0-18) and fibrosis (stage 0-6). Genomic DNA was amplified by polymerase chain reaction and the C282Y mutation identified by restriction with RsaI and electrophoretic separation of restriction fragments. Ten (7.3%) patients had the C282Y mutation. No C282Y homozygous patients were identified. Age, sex distribution, and estimated weekly alcohol consumption were not significantly different between those with and without the mutation. Serum ferritin was higher in the heterozygotes (mean, 339 g/L) compared with homozygous wild types (153 g/L; P ‫؍‬ .0005). In the majority of patients, liver iron was graded 0 out of 4, but hepatocyte iron staining was more commonly present in heterozygotes compared with homozygous normals (30% compared with 4% [P ‫؍‬ .02]). Liver disease was more advanced in those with the mutant allele (mean fibrosis stage: 3.6, compared with wild type: 1.5 [P ‫؍‬ .01]). Cirrhosis was found more often in those with the mutation (40%) compared with those without (8.7%) (P ‫؍‬ .01; odds ratio: 7.6 [1.9-31.2]). There was no significant difference in inflammation scores between heterozygotes and wild type (mean, 5.4 compared with 4

Background-Iron overload is common in the livers of alcoholics and may play a role in disease pathogenesis. An MHC like gene, HFE, has recently been identified that is mutated in most patients with hereditary haemochromatosis (C282Y in 90% and H63D in 45% of the remainder). Aim-To examine the hypothesis that these mutations determine hepatic iron status in alcoholics and play a role in predisposition to advanced alcoholic liver disease. Methods-The HFE gene was genotyped in 257 patients with alcoholic liver disease and 117 locally matched healthy volunteers. In addition, iron staining was scored (0-4) on biopsy specimens from fibrotic/ cirrhotic patients with and without HFE mutations matched for age and sex. Results-Some 15.7% of fibrotic/cirrhotic patients were C282Y heterozygotes compared with 13.7% of controls (p = 0.77). One control and three patients were C282Y homozygotes. Of chromosomes without the C282Y mutation, 68/442 (15.4%) of patients' chromosomes carried the H63D mutation compared with 36/216 (16.6%) of control chromosomes (p = 0.91). Significant (>grade 1) hepatocyte iron staining was seen in 6/23 C282Y heterozygotes and 4/26 H63D heterozygotes compared with 4/23 controls. Conclusions-Possession of a single copy of either of the two HFE mutations influences neither liver iron content nor the risk of fibrotic disease in alcoholics. (Gut 1998;43:262-266)

Background Hepatocellular maturation is characterised by the progessive transition from an architecture in which hepatocyte plates are at least two cells thick to the familiar adult pattern in which liver cell plates are predominantly single‐cell in thickness. A similar process also has been noted during compensatory hyperplasia following damage, or destruction to the hepatic parenchyma. The pathological events that underlie these processes remain inadequately explained. A new morphological approach has been developed to study the maturity of rat neonatal livers in order to identify the factors which govern the structured morphogenesis of the liver in greater detail. Methods Sections of hepatic tissue obtained from the left lateral and right posterior lobes from neonatal rats were studied at 8, 10, 11, 13, 14, 18, 23, and 28 days postpartum. These were mounted, fixed, and stained with haematoxylin and eosin and analysed using a modified point‐counting technique. Following validation of the technique, the proportion of single‐cell plates to double‐cell plates was then calculated at each time point. Results Liver sections from 8‐day neonatal rats had the lowest percentage of single‐cell thick plates of 16.9 ± 4.6% and the lowest standard deviation (mean ± SD). The hepatic architecture had fully matured by 28 days and was characterised by predominantly single‐cell plates (84.6 ± 4.6%) lining the hepatic sinusoids. During the intervening time, the standard deviations increased significantly, peaking between 18–23 days, and reflected the rapidly changing morphology of the liver during this maturation process of the conversion of double‐cell plates to single‐cell plates. Conclusions It is concluded that the process of hepatocellular maturity in the neonatal Sprague‐Dawley rat is reproducibly complete by 28 days and that further studies may now be conducted to determine the anatomical and pathophysiological changes that govern this important transition. Anat. Rec. 248:104–109, 1997. © 1997 Wiley‐Liss, Inc.

These data suggest that ER expression and levels may be implicated in the aetiopathology of VLS and chronic atrophic vaginitis.