Although gender-based medicine is a relatively recent concept, it is now emerging as an important field of research, supported by the finding that many diseases manifest differently in men and women and therefore, might require a different treatment. Sex-related differences regarding the epidemiology, progression and treatment strategies of certain liver diseases have long been known, but most of the epidemiological and clinical trials still report results only about one sex, with consequent different rate of response and adverse reactions to treatment between men and women in clinical practice. This review reports the data found in the literature concerning the gender-related differences for the most representative hepatic diseases.

Background: Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub‐classify cirrhosis.Aim: To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD.Methods: We assessed consecutive patients with biopsy‐proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow‐up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub‐group of patients.Results: Of 437 patients, 32 (7.3%) decompensated and/or died from liver‐related causes during a median follow‐up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0‐F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01‐1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01‐1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02‐47.84) were independent predictors of liver‐related clinical outcomes at standard and competing risk multivariate Cox‐regression analysis.Conclusions: CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.

Given its remarkable property to easily switch between different oxidative states, iron is essential in countless cellular functions which involve redox reactions. At the same time, uncontrolled interactions between iron and its surrounding milieu may be damaging to cells and tissues. Heme—the iron-chelated form of protoporphyrin IX—is a macrocyclic tetrapyrrole and a coordination complex for diatomic gases, accurately engineered by evolution to exploit the catalytic, oxygen-binding, and oxidoreductive properties of iron while minimizing its damaging effects on tissues. The majority of the body production of heme is ultimately incorporated into hemoglobin within mature erythrocytes; thus, regulation of heme biosynthesis by iron is central in erythropoiesis. Additionally, heme is a cofactor in several metabolic pathways, which can be modulated by iron-dependent signals as well. Impairment in some steps of the pathway of heme biosynthesis is the main pathogenetic mechanism of two groups of diseases collectively known as porphyrias and congenital sideroblastic anemias. In porphyrias, according to the specific enzyme involved, heme precursors accumulate up to the enzyme stop in disease-specific patterns and organs. Therefore, different porphyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mitochondrial iron overload and an accumulation of ring sideroblasts in the bone marrow. In line with the complexity of the processes involved, the role of iron in these conditions is then multifarious. This review aims to summarise the most important lines of evidence concerning the interplay between iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron in inherited conditions of altered heme biosynthesis.