Non-invasive assessment of liver fibrosis: it is time for laboratory medicine.

Abstract: Chronic liver diseases (CLDs) represent a major cause of morbidity and mortality worldwide. In all etiologies of CLDs, staging of liver fibrosis is essential for both prognosis and management. Until a few years ago, liver biopsy was the only tool for the diagnosis of liver fibrosis in patients with CLDs. However, liver biopsy is an invasive and costly procedure. More recently, various serum biomarkers and laboratory tests have been proposed as surrogates of liver histology. Due to inadequate diagnostic accuracy or to lack of sufficient validation, guidelines still do not recommend them as a substitute for liver biopsy that is still considered the gold standard for the diagnosis of liver fibrosis. Notably, non-invasive serum biomarkers, when combined, may reduce by 50%-80% the number of liver biopsies needed for correctly classifying hepatic fibrosis. However, liver biopsy cannot be avoided completely, but should be used in those cases in which non-invasive methods show poor accuracy. In this view, serum biomarkers and liver biopsy represent a union between laboratory medicine and hepatology

Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study.

BACKGROUND: Identifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, TB will develop. The objective of this research was to determine how host iron status measured at HIV diagnosis and genotypes related to host iron metabolism were associated with incident TB. METHODS: Archived clinical data, plasma and DNA were analyzed from 1139 adult participants in a large HIV-1, HIV-2 and dual seroprevalent cohort based at the Medical Research Council Laboratories in The Gambia. Incident pulmonary and/or extrapulmonary TB diagnoses a minimum of 28 days after HIV diagnosis were independently re-confirmed using available evidence (n=152). Multiple host iron status biomarkers, Haptoglobin and solute carrier family 11, member 1 (SLC11A1) genotypes were modeled to characterize how indicators of host iron metabolism were associated with TB susceptibility. RESULTS: Hemoglobin (incidence rate ratio, IRR=0.88, 95% CI=0.79-0.98), plasma transferrin (IRR=0.53, 0.33-0.84) and ferritin (IRR=1.26, 1.05-1.51) were significantly associated with TB after adjusting for TB susceptibility factors. While genotype associations were not statistically significant, SLC11A1 associations replicated similar directions as reported in HIV-seronegative meta-analyses. CONCLUSIONS: Evidence of host iron redistribution at HIV diagnosis was associated with incident TB, and genetic influences on iron homeostasis may be involved. Low hemoglobin was associated with subsequent diagnosis of TB, but when considered in combination with additional iron status biomarkers, the collective findings point to a mechanism whereby anemia and iron redistribution are likely due to viral and/or bacteria-driven processes and the host immune response to infection. As a result, iron supplementation may not be efficacious or safe under these circumstances. Clinical and nutritional management of HIV and Mycobacterium tuberculosis co-infected individuals, especially in regions where food insecurity and malnutrition co-exist, may be further improved when the iron-related TB risk factors identified here are better understood and managed to favor host rather than pathogen outcomes