Publications

Background

Severity of hepatic fibrosis is greater in postmenopausal than in premenopausal women, perhaps owing to protective effects of estrogens. However, prior studies of estrogen and liver fibrosis lack serial fibrosis measures, adjustment for age, or longitudinal observations in coinfected populations.

Methods

In a longitudinal cohort of women coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), we assessed fibrosis progression across reproductive age, using validated serum fibrosis markers, aminotransferase platelet ratio index (APRI) and fibrosis 4 (FIB-4). Fibrosis rate was evaluated within each woman as she transitioned from pre- to postmenopause, defined by a biomarker of ovarian function.

Results

The median follow-up (n = 405) was 9.1 years (interquartile range, 5.0-15.2 years), with a median menopausal age of 49 years (47-52 years). When fully controlled for chronologic aging, the fibrosis progression rate was accelerated during perimenopause, as shown using FIB-4 (0.12 units per year faster than during premenopause; 95% confidence interval [CI], .02-.21; P = .01) and APRI (0.05 units per year faster; -.002 to .09; P = .06). Accelerated fibrosis was also observed during postmenopause compared with premenopause, for FIB-4 (0.14 units per year faster; 95% CI, -.01 to .29; P = .07) and APRI (0.07 units per year faster; -.003 to .15; P = .06). Accelerated fibrosis in perimenopause persisted after adjustment for Hispanic ethnicity, antiretroviral use, and alcohol (0.10 FIB-4 units per year faster than during premenopause; 95% CI, .008-.20; P = .03).

Conclusions

In HIV/HCV-coinfected women, hepatic fibrosis accelerates with reproductive aging. Accelerated fibrosis begins in perimenopause, highlighting a previously unrecognized group of women at increased risk for advanced fibrosis and associated complications. Longitudinal analyses of fibrosis rates across reproductive age should be conducted in non-HCV-related liver diseases, given potential implications in a broader spectrum of women.

BACKGROUND

Hispanic patients with cystic fibrosis (CF) have decreased life expectancy compared to non-Hispanic white patients. Pulmonary function is a main predictor of life expectancy in CF. Ethnic differences in pulmonary function in CF have been understudied. The objective was to compare longitudinal pulmonary function between Hispanic and non-Hispanic white patients with CF.

METHODS

This cohort study of 15 018 6-25 years old patients in the CF Foundation Patient Registry from 2008 to 2013 compared FEV percent predicted and longitudinal change in FEV percent predicted in Hispanic to non-Hispanic white patients. We used linear mixed effects models with patient-specific slopes and intercepts, adjusting for 14 demographic and clinical variables. We did sub-analyses by CFTR class, F508del copies, and PERT use.

RESULTS

Hispanic patients had lower FEV percent predicted (79.9%) compared with non-Hispanic white patients (85.6%); (-5.8%, 95%CI -6.7% to -4.8%, P < 0.001), however, there was no difference in FEV decline over time. Patients on PERT had a larger difference between Hispanic and non-Hispanic white patients in FEV percent predicted than patients not on PERT (-6.0% vs -4.1%, P = 0.02). The ethnic difference in FEV percent predicted was not statistically significant between CFTR classes (Class I-III: -6.1%, Class IV-V: -5.9%, Unclassified: -5.7%, P > 0.05) or between F508del copies (None: -7.6%, Heterozygotes: -5.6%, Homozygotes: -5.3%, P > 0.05).

CONCLUSIONS

Disparities in pulmonary function exist in Hispanic patients with CF early in life and then persist without improving or worsening over time. It is valuable to investigate the factors contributing to pulmonary function in Hispanic patients with CF.

Eruption of lymphocyte recovery (ELR) may occur during bone marrow aplasia after chemotherapies. We reviewed the clinical and pathologic features of 12 patients (male-female ratio, 7:5; median age, 61 years) with an atypical ELR histologically mimicking a primary cutaneous T-cell lymphoma such as Sézary syndrome or CD30+ T-cell lymphoproliferative disorder. All the patients displayed an erythematous maculopapular eruption on the trunk and the limbs associated with fever. All but one had received a polychemotherapy for an acute myeloid leukemia (n=10) or a urothelial carcinoma (n=1) before the occurrence of the skin eruption. One had an autoimmune lymphoproliferative syndrome causing chronic agranulocytosis requiring granulocyte colony-stimulating factor injection. In all patients, the skin eruption was associated with a slight increase of white blood cell count followed by bone marrow recovery within the next weeks. All skin biopsies showed a dermal perivascular lymphocytic infiltrate containing atypical medium- to large-sized CD3+, CD4+ and CD8+, CD25+, ICOS+, PD1- lymphocytes with a strong CD30 expression in most instances (n=10), suggesting the recruitment of strongly activated T cells in the skin. In 6 patients, a diagnosis of CD30+ lymphoproliferative disorder or Sézary syndrome was proposed or suspected histopathologically, and only the clinical context allowed the diagnosis of ELR with a peculiar presentation with atypical lymphocytes. We describe a series of patients with an unusual form of ELR characterized by the presence of atypical activated T cells in the skin. On a practical ground, pathologists should be aware of this distinctive and misleading presentation.